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Objectives: Overtraining syndrome (OTS) leads to worsened sports performance and fatigue. The pathophysiology of OTS has not been entirely elucidated, and there is a lack of accurate markers for its diagnosis. Changes in hormonal responses implicated in OTS were stimulated by exercise, which has limited their interpretation. Hence, we aimed to evaluate growth hormone (GH) and prolactin responses to a gold-standard and exercise-independent stimulation test, the insulin tolerance test (ITT)., Design: Volunteers were recruited and divided into OTS-affected athletes (OTS), healthy athletes (ATL), and healthy non-active subjects (NCS) groups, after general and specific inclusion and exclusion criteria., Methods: We evaluated the responses of growth hormone (GH) and prolactin to the ITT, and compared between groups., Results: A total of 51 subjects were included (OTS, n=14, ATL, n=25, and NCS, n=12). OTS disclosed significantly lower basal levels of GH (p=0.003) and prolactin (p=0.048), and GH (p=0.001) and prolactin (p<0.001) responses to ITT (p=0.001), compared to ATL, but similar to NCS. OTS showed a later rise in GH levels in response to hypoglycemia, compared to ATL, but not to NCS. We suggest cutoffs for GH and prolactin levels to aid in the diagnosis of OTS., Conclusions: OTS-affected athletes show reduced GH and prolactin basal levels and responses to a non-exercise stress test compared to healthy athletes, but not to sedentary subjects., (Copyright © 2017. Published by Elsevier Ltd.)

Background: Plurihormonal adenomas (PHAs) represent 10%-15% of all functioning pituitary adenomas. The most frequent hormonal associations are with prolactin and growth hormone (GH). Here we describe a rare case of functional adrenocorticotropic hormone (ACTH) and GH microadenoma and report our findings from a systematic literature review of PHA., Methods: We searched PubMed using the terms "plurihormonal pituitary adenoma," "ACTH GH pituitary adenoma," and "acromegaly AND Cushing's disease". In the 17 articles that were selected for literature review, only 20% (4/20) of patients presented with clinical signs of both diseases. Histologically, 19 were pituitary adenomas composed of two distinct cell populations, while only in 1 case was there evidence of a single cell producing both ACTH and GH. In the case reported here, a 60-year-old woman was incidentally diagnosed with a pituitary microadenoma. Endocrine assessment documented increased levels of insulin-like growth factor 1 and GH; ACTH and cortisol values were within normal ranges. Echocardiography documented ventricular hypertrophy. Because of clinical and biochemical evidence of acromegaly, surgery was recommended. Postoperatively, hormonal replacement therapy was started because of adrenal insufficiency. Her antihypertensive therapy was discontinued due to evidence of normal blood pressure values. Histological examination revealed an ACTH-GH PHA with 2 distinct populations of secreting cells. At 3-year follow-up, the patient showed stable clinical remission and was no longer receiving hormonal replacement therapy., Conclusions: This is an additional case to the 20 previously reported cases of ACTH-GH PHA. Awareness of this relatively rare entity is clinically relevant. The cytogenesis of ACTH-GH PHA remains a matter of debate, and several hypotheses have been postulated., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Pituitary Prolactin (PRL) and Growth Hormone (GH) are separately controlled and sub-serve different purposes. Surprisingly, we demonstrate that extra-pituitary expression in the adult mammalian central nervous system (CNS) is coordinated at mRNA and protein levels. However this was not a uniform effect within populations, such that wide inter-individual variation was superimposed on coordinate PRL/GH expression. Up to 44% of individuals in healthy cohorts of mice and rats showed protein levels above the norm and coordinated expression of PRL and GH transcripts above baseline occurred in the amygdala, frontal lobe and hippocampus of 10% of human subjects. High levels of PRL and GH present in post mortem tissue were often presaged by altered responses in fear conditioning and stress induced hyperthermia behavioral tests. Our data define a common phenotype polymorphism in healthy mammalian brains, and, given the pleiotropic effects known for circulating PRL and GH, further consequences of coordinated CNS over-expression may await discovery.

The aim of the present study was to clarify the effect of photoperiod on secretory patterns of growth hormone (GH) in male goats. Adult male goats were kept at 20°C with an 8-h or 16-h light photoperiod, and secretory patterns of GH secretion were compared. In addition, plasma profiles of prolactin (PRL), insulin-like growth factor-I (IGF-I) and testosterone (T) were also examined to characterize GH secretion. GH was secreted in a pulsatile manner. There was no significant difference in pulse frequency between the 8-h and 16-h photoperiods. However, GH pulse amplitude tended to be greater in the group with the 16-h photoperiod (P = 0.1), and mean GH concentrations were significantly greater in the 16-h photoperiod (P < 0.05). The GH-releasing response to GH releasing hormone was greater in the 16-h than 8-h photoperiod (P < 0.05). Plasma PRL and IGF-I levels were higher in the 16-h than 8-h photoperiod (P < 0.05). In contrast, plasma T levels were lower in the 16-h photoperiod (P < 0.05). These results show that a long light photoperiod enhances the secretion of GH as well as PRL and IGF-I, but reduces plasma T concentrations in male goats., (© 2013 Japanese Society of Animal Science.)

The hypothalamic-growth hormone (GH)-liver axis represents a new concept in endocrine regulation of drug toxicity. Preponderant sex differences are found in liver gene expression, mostly dependent on the sexually dimorphic pattern of GH secretion which is set during the neonatal period by gonadal steroids. We tested if GH-dependent sexually dimorphic liver enzymes and proteins was perturbed by neonatal Bisphenol A (BPA) treatment in female rats. Female rats were sc injected with BPA (50 or 500 μg/50 μl) or castor oil vehicle from postnatal day 1 to 10. At five months serum prolactin, pituitary GH, and serum and liver insulin growth factor-I (IGF-I) were measured by RIA. Major urinary proteins (MUPs) were determined by electrophoresis. Liver Cyp2c11, Cyp2c12, Adh1, Hnf6, and Prlr mRNA levels were determined by real time PCR. Pituitary GH content and liver IGF-I concentration were increased by neonatal BPA treatment, indicating partial masculinization of the GH axis in treated females. GH-dependent female predominant liver enzyme genes (Cyp2c12 and Adh1) and a transcription factor (Hnf6) were downregulated or defeminized, while there were no changes in a male predominant gene (Cyp2c11) or protein (MUP). Our findings indicate that perinatal exposure to BPA may compromise the sexually dimorphic capacity of the liver to metabolize drugs and steroids., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

An experiment was conducted to examine effects of bovine ST (bST) on serum hormone concentrations, pregnancy rates, and offspring performance. Before initiation of a fall breeding period, 75 Rambouillet ewes (68.8 ± 1.5 kg) received an intravaginal insert containing 0.3 g of progesterone (P4) to synchronize onset of estrus. After 12 d, inserts were removed (d 0), and ewes (stratified by BW and age) received either 0 (control, n = 37) or 250 (n = 38) mg of recombinant bST (Posilac, Monsanto, St. Louis, MO, subcutaneously). Ewes were joined with fertile rams 24 h after insert removal. Blood samples were collected from 12 ewes in each treatment group daily from d 0 to 20 after insert removal. Serum IGF-I concentrations were 315 and 437 (± 58) ng/mL in control and bST-treated ewes 2 d after receiving bST (P = 0.02) and remained increased (P < 0.03) in bST-treated ewes throughout the 13-d period (P < 0.05). Serum prolactin (P > 0.10) and estradiol (P = 0.65) were similar between treatments. Serum triiodothyronine (T3) and thyroxine (T4) concentrations were similar (P > 0.20) between treatments from d 0 through 8. Controls had greater (P < 0.04) serum T3 and T4 concentrations than treated ewes did until d 18. Serum P4 was similar (P > 0.10) in control and bST-treated ewes from d 0 through 3 but was increased (P < 0.05) from d 4 to 8 in control ewes. Serum P4 was again similar (P > 0.10) between treatments from d 9 to 20. Serum insulin concentrations were 0.44 and 1.74 (± 0.19) ng/mL in control and bST-treated ewes, respectively, 1 d after receiving bST (P < 0.001) and remained increased (P < 0.03) in bST-treated ewes through d 9 (P < 0.03). Serum glucose was increased (P = 0.003) from d 0 to 10 in bST-treated ewes compared with controls. Thirty-three of 37 (89%) control ewes were pregnant, whereas 27 of 38 (71%) bST-treated ewes were pregnant (P = 0.05). As a percentage of ewes lambing, 61% and 39% of control ewes produced single and twin lambs, respectively, compared with 41% and 59% of bST-treated ewes (P = 0.12). Lamb 60-d adjusted weaning weights were 23.0 and 21.2 (± 0.65) kg for offspring produced by control and bST-treated dams, respectively (P = 0.04). In conclusion, serum IGF-I, insulin, and glucose were greater whereas serum T3, T4, and P4 were less in bST-treated ewes than in controls. Pregnancy rates and offspring adjusted weaning weights were decreased by bST treatment immediately before breeding.

During embryogenesis, the growth hormone-secreting cells (somatotrophs) and the prolactin-secreting cells (lactotrophs) develop from a common progenitor cell (somatomammotroph). Postnatally, in situations when one of these two hormones is oversecreted, often the second hormone is, too. The question posed is whether the increased secretion of growth hormone together with that of prolactin over long periods of time is a risk factor for malignancy.

Objective: To investigate the effect of incretion hormones on growth pituitary adenoma ectomy patients and evaluate its long-term therapeutic efficacy., Methods: A total of 38 growth pituitary adenoma patients were treated by adenoma ectomy between 2002 to 2009 at our hospital. The dynamic concentrations of serum prolactin (PRL), growth hormone (GH), cortisone, adrenocorticotrophic hormone (ACTH) and thyroid function (T3, T4 & thyroid-stimulating hormone) were monitored before and after microsurgery. All cases had been followed up for over one year to evaluate the long-term therapeutic efficacy., Results: The level of GH decreased markedly within one week after ectomy [(2.49 ± 0.22) µg/L vs (9.24 ± 0.56) µg/L, P < 0.05] and remained stable afterwards. Among 22 cases of GH-secreting pituitary adenoma with total removal, the post-operative level of GH dropped below 2.5 µg/L in 11 cases but the other 11 cases did not. And 3 cases were recurrent within 3 years post-operation., Conclusions: The GH level at Week 1 post-operation is one of the major indicators for evaluating the efficacy of surgery. And the level of GH dropping below 2.5 µg/L at Week 1 post-operation may be used as a standard for clinical cure.

Abnormal exposure to steroid hormones within a critical developmental period elicits permanent alterations in female reproductive physiology in rodents, but the impact on the female GH axis and the underlying sexual differences in hepatic enzymes have not been described in detail. We have investigated the effect of neonatal androgenization of female mice (achieved by s.c. injection of 100 μg testosterone propionate (TP) on the day of birth: TP females) on the GHRH-somatostatin-GH axis and downstream GH targets, which included female and male predominant liver enzymes and secreted proteins. At 4 months of age, an organizational effect of neonatal testosterone was evidenced on hypothalamic Ghrh mRNA level but not on somatostatin (stt) mRNA level. Ghrh mRNA levels were higher in males than in females, but not in TP females. Increased expression in TP females correlated with increased pituitary GH content and somatotrope population, increased serum and liver IGF-I concentration, and ultimately higher body weight. Murine urinary proteins (MUPs) that were excreted at higher levels in male urine, and whose expression requires pulsatile occupancy of liver GH receptors, were not modified in TP females and neither was liver Mup 1/2/6/8 mRNA expression. Furthermore, a male predominant liver gene (Cyp2d9) was not masculinized in TP females either, whereas two female predominant genes (Cyp2b9 and Cyp2a4) were defeminized. These data support the hypothesis that neonatal steroid exposure contributes to the remodeling of the GH axis and defeminization of hepatic steroid-metabolizing enzymes, which may compromise liver physiology.

This study characterized endocrine and ionoregulatory responses accompanying seawater (SW) acclimation in Mozambique tilapia (Oreochromis mossambicus). Changes in plasma hormones and gene expression of hormone receptors, putative osmosensors, and ion transporters in the gill were measured. Transfer of freshwater (FW)-acclimated tilapia to SW resulted in a marked elevation in plasma osmolality and a significant rise in plasma growth hormone (GH) levels at 12 hr and 14 days after transfer. Significant reductions in plasma prolactin (PRL(177) and PRL(188)) levels also occurred in SW-transferred fish; no effect of transfer upon plasma cortisol or insulin-like growth factor I was observed. Gene expression of GH receptor increased strongly 6 hr after transfer, whereas PRL receptor was lower than controls at 12 hr. By contrast, mRNA levels of somatolactin and glucocorticoid receptors were unaffected by SW transfer. Osmotic stress transcription factor 1 mRNA levels rose significantly between 3 and 12 hr, whereas the calcium-sensing receptor was unaffected. Aquaporin-3 gene expression was strongly down-regulated during SW acclimation from 12 hr until the conclusion of the experiment. Na(+)/K(+)/2Cl(-) cotransporter gene expression increased significantly 3 hr after transfer, whereas expression of Na(+)/Cl(-) cotransporter, specific to FW-type chloride cells, declined by 6 hr into SW acclimation. The response of Na(+)/H(+) exchanger was less pronounced, but showed a similar pattern to that of the Na(+)/Cl(-) cotransporter. These results suggest that acquisition of hyposmoregulatory mechanisms in Mozambique tilapia entails the coordinated interaction of systemic hormones with local factors in the gill, including hormone receptors, ion transporters, and osmosensors., ((c) 2010 Wiley-Liss, Inc.)

The responses of Mozambique and Nile tilapia acclimated to fresh water (FW) and brackish water (BW; 17 per thousand) were compared following acute salinity challenges. In both species, plasma osmolality increased to above 450 mOsm by 2h after transfer from FW to seawater (SW); these increases in osmolality were accompanied by unexpected increases in plasma prolactin (PRL). Likewise, PRL receptor gene expression in the gill also increased in both species. In Nile tilapia, hyperosmotic transfers (FW to BW and SW) resulted in increased plasma growth hormone (GH) and in branchial GH receptor gene expression, responses that were absent in Mozambique tilapia. Branchial gene expression of osmotic stress transcription factor 1 (OSTF1) increased in both species following transfer from FW to SW, whereas transfer from BW to SW induced OSTF1 expression only in the Nile tilapia. Branchial expression of Na(+)/Cl(-) cotransporter was higher in FW in both species than in BW. Branchial gene expression of Na(+)/K(+)/2Cl(-) cotransporter (NKCC) increased after transfer from BW to SW in Mozambique tilapia, whereas expression was reduced in the Nile tilapia following the same transfer. The difference in the SW adaptability of these species may be related to a limited capacity of Nile tilapia to up-regulate NKCC gene expression, which is likely to be an essential component in the recruitment of SW-type chloride cells. The differential responses of GH and OSTF1 may also be associated with the disparate SW adaptability of these two tilapiine species., (Copyright Elsevier Inc. All rights reserved.)

Objective: It has been suggested that exogenous oestradiol augments ghrelin-induced growth hormone (GH) secretion in postmenopausal women. Whether endogenous oestrogens exert a similar effect during the normal menstrual cycle is not known. The aim of this study was to test the hypothesis that physiological changes in ovarian steroids during the normal menstrual cycle modulate GH and prolactin (PRL) response to ghrelin., Design: Healthy women were studied in three phases of the normal menstrual cycle., Patients: Ten healthy normally cycling women., Measurements: A single dose of ghrelin (1 microg/kg) was administered intravenously in the early and late follicular phases and in the mid-luteal phase of the cycle. Saline was injected in the preceding cycle. Blood samples were taken before ghrelin or saline injection (time 0) and also at -15, 15, 30, 45, 60, 75, 90 and 120 min. The GH and PRL responses were assessed., Results: Serum oestradiol and progesterone concentrations showed the variations of a normal menstrual cycle. After ghrelin administration, in the three phases of the cycle, plasma ghrelin and serum GH and PRL levels increased rapidly, peaking at 30 min and declining gradually thereafter (P < 0.001). There were no significant differences in the hormone levels between the three phases at all time points. No changes in GH and PRL levels were seen after saline injection., Conclusions: These results demonstrate that GH and PRL responses to ghrelin do not change across the menstrual cycle. It is suggested that the action of ghrelin on the pituitary somatotrophs is modulated differentially by endogenous and exogenous ovarian steroids.

Cold therapy is used to relieve pain and inflammatory symptoms. Humoral changes may account for the pain alleviation related to the cold exposures. The aim of the present study was to examine the effects of two types of cold therapy, winter swimming in ice-cold water (WS) and whole body cryotherapy (WBC), on the serum levels of the growth hormone, prolactin, thyrotropin and free fractions of thyroid hormones (fT3, fT4). One group of healthy females (n = 6) was exposed to WS (water 0-2 degrees C) for 20 s and another group (n = 6) to WBC (air 110 degrees C) for 2 min, three times a week for 12 weeks. Blood samples used for the hormone measurements were taken on weeks 1, 4 and 12 before and 35 min after the cold exposures and on the days of the respective weeks, when the cold exposures were not performed. During the WS treatments, serum thyrotropin increased significantly at 35 min on weeks 1 (p < 0.01) and 4 (p < 0.05), but the responses were within the health-related reference interval. During the WS, the serum prolactin measured at 35 min on week 12 was lower than during the control treatment, and no changes in fT3 or fT4 were observed. During the WBC, no changes in the serum levels of the studied hormones were observed during the 12 weeks. In conclusion, repeated WS and WBC treatments for healthy females do not lead to disorders related to altered secretions of the growth hormone, prolactin, thyrotropin, or thyroid hormones.

Cortistatin (CST), a novel neuropeptide, shows high structural homology and functional resemblance with somatostatin. CST binds with high affinity to all somatostatin receptors, and contrary to somatostatin, is also able to bind with MrgX2 and GH secretagogue receptor of ghrelin (GHS-R1) receptors. The aim of the present investigation was to evaluate in vivo the effect of peripheral administration of cortistatin on pituitary hormone release in comparison with somatostatin (SS) treatment. Adult male rats used in the experiment, were given peripheral injection of cortistatin, somatostatin or vehicle. Blood was withdrawn 60 and 120 minutes thereafter. We found short lasting significant decrease of GH concentration as a result of administration of CST and SS when compared with saline injected controls. Prolactin levels were increased 60 min after cortistatin but not to somatostatin injection. There was no effect of CST on both LH and FSH concentration; however, SS administration influenced gonadotropin secretion. We conclude that cortistatin play a regulatory role in pituitary secretion. Moreover, some differences have been found when compared cortistatin to somatostatin. Thus, when analyzing the mechanism of cortistatin activity it is worth to consider the effect of binding with receptors of somatostatin, specific receptor for CST (MrgX2) and GHS-R.

In mice and in rats, reduced levels of the growth hormone secretagogue receptor (GHS-R1a) results in reduced body weight and lower levels of serum insulin-like growth factor I (IGF-I). However, the mechanism leading to these impairments has not been elucidated. Studies in primary cultures of pituitary cells from very young mice have shown that GHS-R1a agonists, including ghrelin, increase expression of the pituitary-specific transcription factor (Pit-1) that is critical for differentiation of pituitary cells into somatotrophs, lactotrophs, and thyrotrophs. Hence, we hypothesized that ablation of Ghsr would reduce Pit-1 expression and as a consequence reduce growth hormone (GH) production explaining the lower body weight of Ghsr-/- mice. Here, we now show that Pit-1 mRNA levels are significantly lower in the pituitary gland of Ghsr-/- mice compared to wild-type littermates and also with advancing age. This Pit-1 loss is associated with reduced GH mRNA and fewer GH producing cells. To determine whether reduced GH is caused by reduced expression of Pit-1 in Ghsr-/- mice, we also measured prolactin (PRL) expression in the pituitary gland and in the circulation. PRL mRNA was significantly reduced in Ghsr-/- mice compared to wild-type littermates and fewer cells expressed PRL. The reduction in expression of both GH and PRL is consistent with a Pit-1 regulated pathway and demonstrates that the GHS-R has an important role in the pituitary gland as a modulator of Pit-1 expression and provides a possible mechanism to explain the lower plasma IGF-1 and modestly reduced body weight exhibited by Ghsr-/- mice. We also believe that lower systemic and lymphoid hormone expression may also account, in part, for the enhanced thymic involution and reduced thymic output in Ghsr-/- mice.

Alteration of neuroendocrine systems has been demonstrated to be involved in the pathology of posttraumatic stress disorder (PTSD). Three months after an earthquake in Northern China, cortisol, growth hormone (GH) and prolactin (PRL) levels were assessed in 34 earthquake survivors with PTSD (according to DSM-IV criteria), 30 earthquake survivors with subclinical PTSD and 34 normal controls. Only earthquake survivors diagnosed with PTSD had significantly higher serum GH levels. Also, we found that earthquake survivors (either with PTSD or subclinical PTSD) had significantly higher serum cortisol levels. We concluded that PTSD might be associated with an increased level of serum GH and traumatic survivors might be associated with a higher level of serum cortisol.

The push-pull perfusions of the infundibular nucleus-median eminence (IN/ME) were made in lactating ewes (n=7) twice, to identify dopamine (DA)-derived salsolinol and the changes in its extracellular concentration in response to suckling. The perfusate collecting period in every ewe consisted of control non-suckling period, 1000-1230 h (five perfusates), and suckling period, 1230-1500 h (next five perfusates). Simultaneously, blood samples were collected from 1000 to 1500 h at 10-min intervals. The perfusate concentrations of salsolinol and DA were measured by HPLC, and plasma prolactin and GH concentrations were assayed by the RIA. Mean concentrations of salsolinol in perfusates collected from the anterior and posterior parts of the IN/ME (according to post-mortem localization of a perfusion site) increased significantly (P<0.05 and P<0.001 respectively) during the suckling period, when compared with those noted during the non-suckling period. While no DA was found in the anterior part, only vestigial amounts of DA were found in a few perfusates collected from the posterior part. Salsolinol was not detected in the IN/ME of ewes 10 weeks after weaning (seasonal anoestrus). Mean plasma prolactin and GH concentrations during suckling were significantly (P<0.001) higher than those noted during the non-suckling period. In conclusion, our current study reveals that salsolinol is present in the IN/ME of lactating ewes and that its extracellular concentration increases during suckling. Moreover, it supports the role of salsolinol as a neurotransmitter involved in the regulatory process of prolactin secretion at least during lactation.

Multiparous beef (1/4 to 3/8 Bos indicus; n = 99) cows were managed to achieve low (BCS = 4.3 +/- 0.1; n = 50) or moderate (BCS = 6.1 +/- 0.1; n = 49) body condition (BC) to determine the influence of bovine (b) ST on the number of follicles, diameter of largest follicle, and serum concentrations of IGF-I, triiodothy-ronine (T3), thyroxine (T4), and prolactin. Beginning 32 d postpartum, cows within each BC were assigned randomly to treatment with or without bST. Non-bST-treated cows received no treatment, and treated cows were administered bST (Posilac, 500 mg, s.c.) on d 32, 46, and 60 postpartum. On d 60, all cows received a controlled internal drug-releasing (CIDR) device for 7 d and PGF(2alpha) at CIDR removal (CIDR-PGF(2alpha)). Blood samples (7 mL) were collected at each bST treatment and d 39 and 67 postpartum. Ultrasound was performed 1 d after CIDR-PGF(2alpha) to determine the number of small (2 to 9 mm) and large (>/=10 mm) follicles and the diameter of largest follicle. Cows treated with bST in low BC had increased (P < 0.05) IGF-I vs. low-BC non-bST-treated cows on d 39, 46, 60, and 67 postpartum. Prolactin and T3 were greater (P < 0.05) in moderate-BC than in low-BC cows on all sample dates. Thyroxine was greater (P < 0.001) in moderate-BC cows on d 46, 60, and 67 compared with low-BC cows. On d 67, bST-treated cows had greater (P < 0.05) T4 compared with non-bST-treated cows. Diameter of the largest follicle 1 d after CIDR-PGF(2alpha) was greater (P < 0.01) in anestrous cows treated with bST than for non-bST-treated anestrous cows. Diameter of the largest follicle was correlated with concentrations of IGF-I (r >/= 0.18; P /= 0.17; P /= 0.20; P

We recently identified a novel hypothalamic neuropeptide stimulating GH release in bullfrogs and termed it frog GH-releasing peptide (fGRP). The fGRP precursor encodes fGRP and its related peptides (fGRP-RP-1, -RP-2, and -RP-3), and fGRP-RP-2 also stimulates GH and prolactin (PRL) release. Cell bodies and terminals containing these neuropeptides are localized in the suprachiasmatic nucleus (SCN) and median eminence, respectively. To understand the physiological role of fGRP and fGRP-RP-2, we investigated the mechanisms that regulate the expression of these neuropeptides. This study shows that melatonin induces the expression of fGRP and fGRP-RPs in bullfrogs. Orbital enucleation combined with pinealectomy (Ex plus Px) decreased the expression of fGRP precursor mRNA and content of mature fGRP and fGRP-RPs in the diencephalon including the SCN and median eminence. Conversely, melatonin administration to Ex plus Px bullfrogs increased dose-dependently their expressions. The expression of fGRP precursor mRNA was photoperiodically controlled and increased under short-day photoperiods, when the nocturnal duration of melatonin secretion increases. To clarify the mode of melatonin action on the induction of fGRP and fGRP-RPs, we further demonstrated the expression of Mel(1b), a melatonin receptor subtype, in SCN neurons expressing fGRP precursor mRNA. Finally, we investigated circulating GH and PRL levels after melatonin manipulation because fGRP and fGRP-RP-2 stimulate the release of GH and GH/PRL, respectively. Ex plus Px decreased plasma GH and PRL concentrations, whereas melatonin administration increased these hormone levels. These results suggest that melatonin induces the expression of fGRP and fGRP-RP-2, thus stimulating the release of GH and PRL in bullfrogs.

Objective: Lanreotide Autogel 120 mg (ATG120; Ipsen S.p.A, Milan, Italy) is a high-dose, sustained-release aqueous gel formulation, supplied in a prefilled syringe and given by deep subcutaneous injection. The aim of this study was to compare efficacy and tolerability of ATG120 given every 4-8 weeks with those of octreotide LAR (o-LAR) given every 4 weeks. DESIGN PATIENTS AND INTERVENTION: A phase III multicentre Italian open clinical study of 23 acromegalic patients (15 female, 8 male). All patients had received o-LAR for 6-18 months and, after 3 months wash out, ATG120 was given every 6 weeks for a total of four injections (Period 1). Then the interval between ATG120 injections was adjusted according to three different schemes: every 4, 6 or 8 weeks depending on GH levels (GH > 2.5 microg/l; 1 < GH

Comparative investigations of somatotropin and prolactin contents in the fluid of antral follicles and blood serum of cows in different phases of the oestrous cycle were performed. The somatotropin concentration in the fluid was shown to rise with increasing the follicle diameters from 3-5 to 6-10 mm in the follicular phase and to decrease in follicles of diameter 11-20 mm in the luteal phase. The prolactin concentration was higher in the fluid of follicles 11-20 mm in diameter than in those of 3-5 mm in diameter in the follicular phase and did not depend on the follicle size in the luteal phase. Concurrently, the prolactin content in follicles 3-5 mm in diameter was higher in the luteal than follicular phase of the cycle. As compared to the follicular phase, an increase in the prolactin concentration in the bovine blood serum during the luteal phase was also found. The data obtained indicate that changes in the somatotropin and prolactin contents in the follicular fluid are related to processes regulating growth and development of antral follicles depending on the phase of oestrous cycle and to changes in the blood hormone concentrations as well.

Rationale: Serotonergic pharmacological challenges have failed to produce consensual results in patients with obsessive-compulsive disorder (OCD), suggesting a heterogeneous 5-hydroxytryptamine (5-HT) activity in this disorder., Objectives: The aim of this study was to compare the neuroendocrine response to a serotonergic challenge in OCD patient responders (RP) and nonresponders (NR) to serotonin reuptake inhibitors treatment and healthy volunteers., Materials and Methods: Thirty OCD treatment NR, 30 RP, and 30 controls (CN) matched for sex and age were included. Each subject received 20 mg of intravenous citalopram. Prolactin, cortisol, and growth hormone plasma concentration were measured at times-20, 0, 20, 40, 60, 80, 100, 120, 140, and 160 min after the onset of citalopram infusion., Results: Citalopram did not induce anxiety or OCD symptoms in patients. Citalopram was associated with stronger prolactin response in the CN group (maximal percentage variation [max%Delta] = 65.76 +/- 105.1) than in NR (max%Delta = 17.41 +/- 31.06) and RP groups (max%Delta = 15.87 +/- 31.71; p = 0.032; Friedman chi (2) = 6.87; df = 2). On the other hand, cortisol response did not differ between CN and RP groups and was blunted in the NR group (NR max%Delta = 20.98 +/- 58.14 vs RP max%Delta = 47.69 +/- 66.94; CN max%Delta = 63.58 +/- 88.4; p = 0.015; Friedman chi (2) = 8.60; df = 2)., Conclusions: Compared to CN, both treatment RP and NR patients showed blunted prolactin response to citalopram, but only NR patients showed an attenuated cortisol response, suggesting a more disrupted central serotonergic transmission in this group.

Background: Radiation induces time-dependent loss of anterior pituitary function, attributed to damage of the pituitary gland and hypothalamic centres. The development of growth hormone deficiency (GHD) in irradiated acromegaly patients is not well defined., Objective: Detailed analysis of spontaneous 24-h GH and prolactin (PRL) secretion in relation to other pituitary functions and serum IGF-I concentrations in an attempt to find criteria for GHD in acromegalic patients with a GH response < 3 microg/l during the insulin tolerance test (ITT)., Design: Plasma hormone profiles obtained by 10 min sampling for 24 h in postoperatively irradiated acromegalic patients, compared with patients cured by surgery only and matched healthy controls., Setting/participants: University setting. Fifteen subjects in each group., Outcome Measures: GH and PRL secretory parameters quantified by deconvolution, cluster, cosinor and approximate entropy (ApEn) analyses, IGF-I concentrations., Results: Irradiation attenuated pulsatile secretion of GH and PRL, but total PRL secretion was unchanged. GH and PRL secretory regularity were diminished. Circadian timing remained intact. Pulsatile GH secretion and IGF-I were correlated (R = 0.30, P = 0.04). Criteria of pulsatile GH secretion = 12 microg/l/24 h and ApEn = 0.800 separated 12 of 15 irradiated patients from all others., Conclusion: Irradiated acromegaly patients with a subnormal GH response to ITT have very limited spontaneous GH secretion, with specific attenuation of the size of GH bursts and a highly irregular pattern, but with retained diurnal properties. These patients are thus likely GH-deficient and might benefit from GH replacement.

A decline in circulating progesterone concentration plays an important role in the ethiopathogenesis of pseudopregnancy in the bitch. Because growth hormone (GH) and prolactin (PRL) are essential for normal mammogenesis and the secretion of these hormones is influenced by changes in the circulating progesterone concentration, the purpose of this study was to investigate the effects of mid-luteal phase ovariectomy on the 6-h pulsatile plasma profiles of GH and PRL and the basal plasma concentrations of GH, PRL, and insulin-like growth factor-I (IGF-I) in six beagle bitches. Ovariectomy was followed by only mild or covert signs of pseudopregnancy. The sharp decrease of the plasma progesterone concentration was accompanied by decreased basal plasma concentrations of GH and IGF-I and a rise in basal plasma PRL concentration. GH and PRL were secreted in a pulsatile fashion both prior to and after ovariectomy. The mean basal plasma GH concentration was significantly higher before ovariectomy than on days 1 and 7 after ovariectomy. The mean area under the curve above the zero level (AUC(0)) for GH was significantly higher before than at 7 days after ovariectomy. The mean area under the curve above basal level (AUC(b)) and the frequency of GH pulses at 7 days after ovariectomy were significantly higher than before and 1 day after ovariectomy. Both the mean basal plasma PRL concentration and the mean AUC(0) for PRL increased after ovariectomy. In conclusion, ovariectomy of bitches in the mid-luteal phase stops progesterone-induced GH release from the mammary gland, as evidenced by the lowering of basal plasma GH levels, the recurrence of GH pulsatility, and the lowering of circulating IGF-I levels. The sudden lowering of plasma progesterone concentration is probably a primary cause of a prolonged increase in PRL secretion. These observations underscore the importance of similar, albeit less abrupt, hormonal changes in the cyclical physiological alterations in the mammary gland and in the development of pseudopregnancy.

This study compared prolactin (PRL) and growth hormone (GH) responses to hypoglycemia in premenopausal females with systemic sclerosis (SSc) and psoriatic arthritis (PsA) with those in matched healthy controls. No differences were found in glucose and GH responses to hypoglycemia in both groups of patients compared to controls. SSc patients had lower PRL response (P < 0.05) to hypoglycemia compared to controls. PRL response tended to be lower also in PsA patients, however the difference did not reach level of statistical significance (P = 0.11). The present study showed decreased PRL response to hypoglycemia in premenopausal females with SSc.

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

Taking into account the role played by the neuroendocrine network in affecting the early development of the immune response, the present study aims to assess neonatal immunity in piglets by testing peripheral lymphocyte age-related changes in relationship to plasma levels of some relevant immunoregulatory hormones, such as growth hormone (GH), prolactin (PRL) and cortisol. For this purpose, we studied the peripheral lymphocyte age-related changes in relationship to plasma levels of GH, PRL and cortisol in conventional piglets from birth (day 0) to 41 days of age. A significant decrease was observed in the total number of lymphocytes at day 0, with a subsequent constant increment up to 41 days of age. Concomitantly, the number of T cell subsets (mainly CD8(+) cells and double positive CD4(+)CD8(+)) was low at birth, with strong increments between the 19th and 41st days of life. The CD4(+) T cell number subset was less diminished at birth than that of CD8(+), albeit with significant increments in the post-weaning period. Of interest, gammadelta T cells, which are more involved in innate immune efficiency, displayed the same trend as CD8(+) T cells from birth to the 41st day of life. From day 0 up to the 19th day, significant inverse correlations were found between T cell subsets and GH or PRL or cortisol, albeit with more significant inverse correlations with cortisol. The high levels of GH and PRL in the pre-weaning period may be due to the fact that they have to counteract the cortisol-mediated negative effect on lymphocyte production and development. These findings suggest that stress condition occurs at birth with decreases in the immune parameters, in the same way as in human newborns, with a subsequent gradual normalisation and immune development, as shown by decreased cortisol, GH and PRL normalisation and concomitant increments in T cell subsets.

This work analyzes the effect of social isolation of growing male rats on 24-h changes of plasma prolactin, growth hormone, ACTH and leptin, and on plasma and adrenal corticosterone concentrations. At 35 days of life, rats were either individually caged or kept in groups (6-8 animals per cage) under a 12:12 h light/dark schedule (lights on at 08:00 h). A significant arrest of body weight gain regardless of unchanged daily food intake was found in isolated rats after 2 weeks of isolation. On the 4th week, rats were killed at 6 time intervals during a 24-h cycle, beginning at 09:00 h. In isolated rats the 24-h pattern of all parameters tested became distorted, as assessed by Cosinor analysis. When analyzed as a main factor in a factorial analysis of variance, isolation decreased plasma prolactin and growth hormone, increased plasma leptin and corticosterone while decreased adrenal corticosterone. Plasma corticosterone levels correlated significantly with plasma ACTH and with adrenal corticosterone levels in group-caged rats only. These changes can be attributed to an effect of mild stress on the endogenous clock that modulates the circadian hormone release.

Nocturnal hormone profiles were measured in patients with schizophrenia with predominantly negative symptoms both under drug-free baseline conditions and after subchronic administration of the atypical antipsychotic olanzapine, with the aim of characterizing its pharmacological properties on the neuroendocrine level. The following hormones were studied in the sleep laboratory under polysomnographic control: adrenocorticotrophic hormone, cortisol, growth hormone (GH), prolactin, testosterone, and melatonin. Blood samples were taken at regular time intervals over the night, and serum concentrations of the hormones were determined. Ten patients completed the study, two of them were excluded from analysis due to incomplete hormone profiles. The dynamics of baseline nocturnal hormone secretion were similar to the patterns known from healthy subjects. After the treatment period of about 4 weeks, hypothalamic-pituitary-adrenal axis activity was reduced with decreased cortisol plasma levels compared to baseline conditions. Olanzapine induced a moderate prolactin elevation. The characteristic GH peak around sleep onset, clearly present under baseline conditions, was markedly reduced after treatment. Testosterone and melatonin secretion were not significantly altered. In conclusion, although interpretation is difficult in some cases due to interference with indirect effects of olanzapine administration and the consequences of the clinical course of the underlying schizophrenic disorder, the neuroendocrine findings are consistent with the receptor-binding profile of olanzapine where, beside the D(2) antagonism, the antiserotonergic properties are most important.

In most teleost fishes, prolactin (PRL) plays a key role in freshwater (FW) adaptation, whereas growth hormone (GH) is involved in seawater (SW) adaptation in salmonids and certain euryhaline species including the tilapia, Oreochromis mossambicus. Consistent with its osmoregulatory activity, PRL release increases in response to physiologically relevant reductions in extracellular osmolality. When dispersed PRL and GH cells from FW-acclimatized fish were incubated in media of varying osmolalities, PRL release increased significantly in response to a 12% reduction in medium osmolality during 1 and 4h of exposure. By contrast, cells from SW-acclimatized fish responded only to a 24% reduction in osmolality. Growth hormone release on the other hand increased whether medium osmolality was reduced or raised. Cell volume increased together with PRL release during the perifusion of dispersed PRL cells in direct proportion to the reduction in medium osmolality. Growth hormone release increased whether GH cell volume increased or decreased. In in vivo studies, circulating PRL levels increased as early as 1h after the transfer of fish from SW to FW, whereas GH levels remained unchanged during 24h of acclimatization. These results indicate that while PRL and GH cells are osmosensitive, the PRL cells respond to reductions in extracellular osmolality in a manner that is consistent with PRL's physiological role in the tilapia. While the rise in GH release following the reduction in osmolality is of uncertain physiological significance, the rise in GH release with the elevation of medium osmolality may be connected to its role in SW adaptation.

Leptin may play a role in the endocrine-metabolic processes that guarantee the physiological course of lactation in dairy cattle. This study was aimed at determining the changes in plasma concentrations of leptin and some of the main hormones and metabolites involved in the lactogenetic process in high-yielding dairy cows throughout lactation; we also wanted to assess whether leptin secretion is subjected to seasonal influences. Blood samples were collected from 23 Italian Friesian dairy cows from the end of a lactation to the ninth month of the subsequent one; in addition, blood was sampled from 47 dairy cows in different phases of lactation during February and July. Plasma concentrations of leptin, growth hormone (GH), insulin, prolactin (PRL), glucose, non-esterified fatty acids (NEFA) and urea were quantified by either validated radioimmunoassay (RIA) or enzymatic colorimetric methods. At the beginning of lactation, GH concentrations significantly increased, while a significant reduction occurred in leptin and insulin. This endocrine condition, such as the significant increase in NEFA plasma concentrations, is indicative of a marked lipid mobilization. In the more advanced stages of lactation, when both energy and protein balances become positive, leptin plasma concentrations increased, whereas GH and NEFA concentrations declined. During the summer months, a significant increase in leptin plasma concentrations, irrespective of the phase of lactation, was observed. Collectively, our findings suggest that, in dairy cows, leptin may represent a 'metabolic signal' of animal's status of fattening and nutritional level; in addition, leptin seems to be influenced by photoperiod and environmental temperature.

The present study was undertaken to assess whether chronic exposition to cadmium (Cd, 0.133 mM per liter for 2 months) through drinking water may affect the lipid contents in the pituitary anterior lobe (PAL) of adult male Wistar rats. As compared to metal non-exposed controls, PALs exposed to cadmium showed an increase in total phospholipid contents, which was associated to an increase of the incorporation of [1-14C]-methyl choline into phosphatidylcholine and of [U-14C]-glucose into total phospholipids. The incorporation of [1-14C]-methyl choline into sphingomyelin was not changed. Incorporation of [1-14C]-acetate into total fatty acids also increased but incorporation of [1-14C]-acetate into cholesterol did not change. The activity of phospholipase D decreased both in PALs from Cd exposed rats and in PAL dispersed cells treated with Cd in the culture medium from Cd non-exposed rats. In PALS from Cd exposed rats, a decrease of serum prolactin and growth hormone concentrations was determined. The results shown that cadmium modifies the lipid contents of pituitary gland and directly or indirectly the levels of prolactin and growth hormone in serum.

Thyrotoxicosis due to Graves disease is a relatively common endocrine disorder. The occurrence of a prolactinoma with co-secretion of growth hormone (GH) is on the other hand, rare. We report the rare co-existence of Graves' disease in a patient with macroprolactinoma and GH hypersecretion and describe the successful response to medical therapy with dopamine agonist and antithyroid therapy. We hypothesize that hyperprolactinaemia played a role in promoting autoimmune thyroid disease in our patient and that treatment of hyperprolactinaemia may have been important in suppressing autoimmune disease activity in Graves' disease. This case also reflects on the close and complex interactions between thyroid hormones, prolactin (PRL), GH and testosterone (T).

In rodents, corticosterone (cortisol in humans) facilitates cocaine self-administration purportedly via enhancement of dopaminergic activity in the brain. This study sought to assess central dopaminergic effects of cortisol in humans and to compare them to those of cocaine. Twelve cocaine-dependent individuals received an intravenous bolus of cortisol (0.5 and 0.2 mg/kg; n=6 for each dose) and cocaine (0.2 mg/kg) in a double-blind randomized placebo-controlled and counterbalanced fashion. Their plasma was assayed over the next 120 min for prolactin and growth hormone (GH), which are two neuroendocrine indices of dopaminergic function. Cortisol injections produced significant increases in GH, while cocaine resulted in significant decreases in prolactin. Placebo administration was associated with gradual declines in prolactin, but the levels at the 90- and 120-min time points were significantly lower after cocaine than after placebo infusion. These different neuroendocrine response profiles point to important differences between dopaminergic effects of cortisol and cocaine.

Galanin-like peptide (GALP) stimulates the release of gonadotropin-releasing hormone in rodent and primate species. The widespread distribution of GALP fibers in the hypothalamus suggests that this neuropeptide may influence hypophysiotropic factors that control other aspects of adenohypophysial function. Here we studied the effects of intracerebroventricular administration of GALP on serum levels of growth hormone (GH) and prolactin (PRL) in adult male monkeys. The animals (n = 5) were orchidectomized and implanted with testosterone-containing Silastic capsules to maintain the circulating testosterone levels (approximately 9 ng/ml) within the physiological range. The animals were implanted with an intracerebroventricular cannula and venous catheter for continuous access to the cerebroventricular and the venous circulation, respectively. GALP (500 microg), or vehicle alone, was administered as a bolus intracerebroventricular injection, and sequential blood samples were collected at 20-min intervals for 3 h before and after the injections. Within 20 min following GALP injection, the GH concentrations increased 3.5-fold, and a peak level (12.9 +/- 2.7 ng/ml) was observed 40 min after injection. The GH levels remained elevated until 60 min after injection and thereafter declined to values similar to those observed at 0 min. The GH concentrations were not changed by vehicle alone. A decline in PRL levels was observed following GALP administration, with significantly reduced concentrations occurring between 60 and 120 min following the injection of the neuropeptide. We conclude that in the monkey GALP is a potent secretagogue for GH and an inhibitor of PRL secretion and that GALP may, therefore, interact with the hypothalamic circuitry involved in the regulation of these pituitary hormones., (Copyright 2005 S. Karger AG, Basel.)

Objective: Prolactin (PRL) and growth hormone (GH) are pituitary hormones with immunomodulating properties. Their upregulated secretion may play a role in the pathogenesis of chronic inflammatory diseases. We evaluated PRL and GH responses to secretion stimulus in patients with rheumatoid arthritis (RA) and ankylosing spondylitis (AS)., Methods: Insulin hypoglycemia (0.1 IU/kg) was induced in 15 women with RA, 18 men with AS, and healthy controls matched for age, sex and body mass index. Plasma concentrations of glucose, PRL, GH, interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-a) were analyzed., Results: RA patients had significantly lower area under the curve (AUC) of PRL (p = 0.049) compared to RA controls. During hypoglycemia double or higher increase of plasma PRL occurred in 5 RA (33%) patients and in 8 RA controls (57%). Using the General Linear Model procedure, no significant differences in PRL or GH responses were observed in patients with RA and AS. TNF-a was higher in patients with RA compared to RA controls (p < 0.05). There was no significant difference in TNF-a concentrations between AS patients and AS controls. IL-6 was higher in RA patients compared to controls (p < 0.05) and in AS patients compared to controls (p < 0.01). Significant positive correlation was found between TNF-a levels and AUC of PRL in AS patients (r = 0.46, p = 0.047), but not in the 2 control groups or in RA patients., Conclusion: Our results indicate no upregulated PRL or GH responses to stimulation in premenopausal women with RA or men with AS.

In vivo and in vitro effects of prolactin (PRL) and growth hormone (GH) on plasma levels of lysozyme and ceruloplasmin were examined in the rainbow trout (Oncorhynchus mykiss). Hypophysectomy had no effect on the plasma lysozyme level. Implantation of PRL- or GH-containing cholesterol pellets increased the lysozyme level in a dose-related manner. After hypophysectomy and sham operation, plasma ceruloplasmin was elevated above the level in intact fish, suggesting inflammation caused by the surgery. PRL or GH treatment significantly attenuated the increased level of ceruloplasmin in the operated fish. Expression of lysozyme mRNA was detected in the leucocytes isolated from the peripheral blood by RT-PCR. In vitro administration of PRL or GH showed no effect on the proliferation of isolated leucocytes or on the total protein content; however, lysozyme activity in the medium increased in a dose-related manner. These results suggest that PRL and GH directly stimulate lysozyme production without affecting the proliferation of leucocytes, and the attenuated ceruloplasmin level increased in response to inflammation.

To assess the effect of social isolation of growing rats on 24-h rhythmicity of circulating prolactin and growth hormone (GH) levels and submaxillary lymph node immune responses, male Wistar rats were either individually caged or kept in groups (4-5 animals per cage) for 30 d starting on d 35 of life. Plasma prolactin and GH levels, and submaxillary lymph node lymphocyte subset populations, interferon (IFN)-gamma release and mitogenic responses to concanavalin A (Con A) and lipopolysaccharide (LPS) were determined at six time intervals during the 24 h span. Social isolation brought about changes in mean values and 24-h pattern of plasma prolactin and GH levels and lymph node immune responses. After isolation, prolactin and GH mean values decreased, and lymph node T, B, non T-non B, CD8+, and CD4+-CD8+ cells augmented, whereas lymph node CD4+/CD8+ ratio, IFN-gamma release and mitogenic responses decreased. Social isolation resulted in disruption of 24 h rhythmicity of every immune parameter tested. CD4+/CD8+ ratio, IFN-gamma release and Concanavalin A (Con A) and lipopolysaccharide (LPS) responses correlated significantly with plasma prolactin or GH levels while T/B ratio correlated with plasma prolactin levels only. B, non T-non B, and CD4+-CD8+ cells correlated negatively with plasma prolactin. Modifications in mean value and 24-h rhythmicity of plasma prolactin and GH levels are presumably involved in the effect of social isolation on immune responsiveness.

This study was designed to compare growth hormone, cortisol and prolactin responses to physical exercise in depressed patients and healthy comparison subjects. Patients fulfilled the DSM-IV diagnostic criteria for current major depressive disorder; subjective depressive symptoms were rated with Montgomery-Asberg Depression Rating Scale (MADRS) immediately before the experiment. Growth hormone, cortisol and prolactin were measured before and immediately after physiologically stressful bicycle cardiopulmonary exercise test. After exercise, there were three additional hormone measurements, with 30-min intervals. No significant difference was found in baseline growth hormone, cortisol or prolactin levels between patients and the control group. Plasma growth hormone and cortisol levels increased significantly during physical exercise in both patients and controls and returned to baseline in 90 min. There was no significant difference in growth hormone or cortisol responses to physical exercise between the two groups. However, prolactin levels increased only in the depressed patients group during the exercise. We hypothesize that acute exercise may have a stronger effect on serotonin (5-HT) release in depressed patients, which is reflected in increased plasma prolactin concentration.

Objective: We have previously reported that acquired prolactin deficiency (APD) is a marker for severe hypopituitarism and observed a high prevalence of APD in patients treated for Cushing's disease. Recovery of GH secretion is recognized to occur in a proportion of patients treated for Cushing's disease after the effects of glucocorticoid excess on GH secretion have subsided. The aim of this study was to investigate further the association between APD, treated Cushing's disease and, in particular, to determine whether recovery of GH secretion may occur in these patients., Methods: Fifty-seven patients (42 female), in remission after treatment for Cushing's disease, were studied. The cohort comprised 13 patients with, and 44 without APD. APD was defined as a serum prolactin persistently below the detection limit of the assay. Severe GH deficiency was defined as a peak GH response of less than 9 mU/l during a GH stimulation test. Age and gender did not significantly differ between subgroups., Results: Of the 13 patients with APD, a macroadenoma was present in one patient, a microadenoma was present in 10, no lesion was detected in one, and in one patient (treated with an yttrium implant) the size of the tumour was unknown. Of the 28 patients who did not have APD, who were treated with primary surgery a microadenoma was present in 23 and a macroadenoma was present in five. Detailed pituitary imaging was not available in 16 patients who did not have APD, who were treated with primary external XRT. Deficiencies of GH, TSH, LH/FSH (P < 0.0001) and ADH (P = 0.006) status, by conventional testing, were present more frequently in the APD subgroup. In contrast, the prevalence of ACTH deficiency after treatment was not different between the APD and non-APD groups. However, the requirement for additional therapy, targeting the pituitary or adrenal gland, after primary treatment, in those patients not rendered ACTH-deficient, was significantly greater in the APD compared with the non-APD groups (P = 0.003). After pituitary surgery, a significant correlation between peak GH response and interval since remission of Cushing's syndrome was found in the subgroup without APD (r = 0.4, P = 0.04). Four patients who did not have APD, who had documented severe GHD in the immediate postoperative period displayed normalization of GH secretion, when re-tested after a mean interval of 27.2 months. In contrast, no patient with APD after pituitary surgery demonstrated a detectable GH response after up to 132 months of follow-up. No patient with APD showed recovery of prolactin secretion by the time of the most recent measurement (mean 57 months). All 10 patients who developed APD immediately after pituitary surgery had undergone a radical procedure (either a subtotal or total hypophysectomy). In contrast, of 28 patients with Cushing's disease who did not develop APD, only four underwent radical surgery (P < 0.0001). Seven of 14 patients (50%) who underwent a radical operation and two of 20 treated by selective adenomectomy (10%) required additional treatment to achieve control of Cushing's syndrome (P = 0.04)., Conclusion: In the presence of APD, patients with Cushing's disease do not experience recovery of GH secretion after treatment, even after the effects of glucocorticoid excess subside. In the absence of APD, GH status may normalize after successful surgical treatment. Although a marker for severe hypopituitarism, APD does not indicate success of treatment of Cushing's disease and may be associated with detectable ACTH secretion from residual corticotroph adenoma activity. APD after pituitary surgery for Cushing's disease occurs only after a radical operation. When a selective adenomectomy is not possible, control of Cushing's disease by operation is less frequent and when achieved, is more often at the cost of hypopituitarism. The optimal management of such patients requires further study.

This study tested a hypothesis that the enhancement of the prolactin (PRL) concentration within the central nervous system (CNS) disturbs pulsatile luteinizing hormone (LH) and growth hormone (GH) secretion in rams that are in the natural breeding season. A 3h long intracerebroventricular (icv.) infusion of ovine PRL (50 microg/100 microl/h) was made in six rams during the daily period characterized by low PRL secretion in this species (from 12:00 to 15:00 h); the other six animals received control infusions during the same time. Blood samples were collected from 9:00 to 18:00 h at 10 min intervals. A clear daily pattern of LH secretion was shown in control animals, with the lowest concentration at noon and an increasing basal level around the time of sunset (P < 0.001). No significant changes in LH concentration occurred in PRL-infused animals and the concentration noted after infusion of PRL was significantly (P < 0.05) lower than after the control infusion. The frequency of LH pulses tended to decrease in rams after PRL treatment. The changes in LH secretion clearly carried over to the secretion of testosterone in the rams of both groups. The GH concentrations changed throughout the experiment in both groups of rams, being higher after the infusions (P < 0.001). However, the mean GH concentration and GH pulse amplitude noted after PRL infusion were significantly lower (P < 0.001 and P < 0.05, respectively) from those recorded in the control. The continued fall in PRL secretion observed in rams following PRL infusion (P < 0.05 to P < 0.001) indicates a high degree of effectiveness of exogenous PRL at the level of the CNS. In conclusion, maintenance of an elevated PRL concentration within the CNS leads to disturbances in the neuroendocrine mechanisms responsible for pulsatile LH and GH secretion in sexually active rams.

Dexamethasone suppression (DST), thyroid-stimulating hormone (TSH) and prolactin (PRL) responses to thyrotropin-releasing hormone (TRH) and growth hormone (GH) response to L-DOPA tests were evaluated in 19 depressed inpatients before the commencement of the antidepressant treatment and after the clinical response to examine: (i) the functional relationships among the hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axis and dopaminergic system in depression, (ii) any alterations in these hormonal functions with the antidepressant treatment. TSH responses to TRH showed a tendency to increase from pre- to posttreatment period, while TRH-induced PRL and L-DOPA-induced GH responses did not change with treatment in depressed patients who responded to the treatment. Females showed significantly higher TSH and PRL responses to TRH compared to males. No interconnections were found among the responses in DST, TRH stimulation test and L-DOPA-induced GH test in the patients. The results do not support the interrelations between the abnormalities in the HPT and HPA axes and central dopaminergic activity in depression.

Objective: We tested the impact of commencement of GH replacement therapy in GH-deficient (GHD) adults on the circulating levels of other anterior pituitary and peripheral hormones and the need for re-evaluation of other hormone replacement therapies, especially the need for dose changes., Methods: 22 GHD patients were investigated in a double-blind randomized study and 90 GHD patients in an open study at baseline and after 6 and 12 months of GH replacement therapy., Results: In the placebo-controlled trial, the FT(3) levels increased after 6 months in the GH-treated group, and in the open study the FT(3) levels tended to increase. Other hormone concentrations did not change in either part of the study. Four patients required an increase in thyroxine dose, while 2 patients needed dose reduction. One originally euthyroid patient required thyroxine replacement. Two patients with originally conserved pituitary-adrenal function developed ACTH insufficiency. The hydrocortisone dose was increased in 1 and decreased in 1 of the 66 patients with secondary hypocortisolism. None of the females required any adjustment of sex hormone replacement therapy. Two of 37 males needed dose increase of testosterone, while 1 needed dose reduction., Conclusion: GH replacement therapy required dose adjustments regarding other hormone replacement therapies in 12.2% (n = 11), while initiation of new hormone replacement was performed in 3.3% (n = 3) of the 90 patients during the 1-year follow-up. Monitoring of pituitary hormone axes is advisable after commencement of GH replacement therapy, since changes of hormone replacement therapy was observed in a small but clinically significant number of patients., (Copyright 2004 S. Karger AG, Basel)

Objectives: Calorie restriction has been associated with anorexia in growing individuals, but the mechanisms involved are not known. Also, the effects of carbohydrates and lipid restriction in growing individuals were not studied. The aim of this study was to determine whether 66% calorie restriction (lipids and carbohydrates) differentially affects growing rats of the Wistar or Lewis strains., Methods: Growing male Wistar and Lewis rats were subjected to 66% calorie restriction for 4 weeks. Plasma prolactin, growth hormone (GH), and adrenocorticotropic hormone (ACTH) levels were measured by specific radioimmunoassays. Likewise, lymphocytes from submaxillary lymph nodes were aseptically obtained to study absolute number of lymphocytes, cell surface markers (CD4+, CD8+, CD4+CD8+, B, and T cells), and proliferation., Results: The body weight gain was lower in Lewis than in Wistar rats and was blunted in both strains by calorie restriction. Wistar and Lewis rats exhibited differential patterns of plasma prolactin, ACTH, and GH levels as well as proliferative capacities of T and B cells and their distribution in the submaxillary lymph nodes. Calorie restriction increased plasma prolactin and ACTH levels in Lewis as compared with Wistar rats. However, the plasma GH levels were diminished in both strains of rats by calorie restriction. All changes in plasma prolactin ACTH and GH levels seemed to correlate with the modifications observed in the distributions of T and B subsets in the submaxillary lymph nodes as well as in their proliferative capacity., Conclusions: Calorie restriction differentially modifies the secretory patterns of prolactin, GH, and ACTH in Lewis and in Wistar rats. These changes may explain, at least in part, the associated modifications in the proliferative capacity of submaxillary lymph node lymphocytes and in their distribution., (Copyright 2004 S. Karger AG, Basel)

Objective: Prolactin deficiency has been the subject of many scientific studies, but there is a paucity of information regarding prolactin deficiency in humans. In this report, adults with disease of the hypothalamic-pituitary axis (HPA) were studied to determine the prevalence of severe acquired prolactin deficiency (APD) and the pathophysiological characteristics associated with it., Patients and Methods: APD was defined as a serum prolactin level persistently below the detection limit of the assay, i.e. less than 50 mU/l (normal range: male 85-444, female 85-530). Patients with a diagnosis of acromegaly, prolactinoma or with congenital or drug induced prolactin deficiency were excluded. Three hundred and sixty-nine patients (190 women, age range 17-79 years) with disease of the HPA, meeting the specified criteria were identified., Results: Twenty-two (13 women, age range 29-76 years), showed evidence of APD. Thirteen of the 22 patients with APD had been treated for Cushing's disease. In all, 62 patients treated for Cushing's disease were identified, resulting in a prevalence of APD in treated Cushing's disease of 20.97%. Excluding treated Cushing's disease, the prevalence of APD in the remainder of the cohort was 2.93%. Nineteen patients with APD (86.4%) and 183 without APD (52.7%) underwent surgery in the region of the HPA (P = 0.0042). In contrast, nine patients with APD (40.9%) and 283 without APD (80.4%) had received radiotherapy, with fields which included the HPA (P < 0.001). No patient with isolated APD was identified. All patients with APD had evidence of severe GH deficiency (GHD) with a peak GH response to provocative stimuli of < 1.6 mU/l and a median IGF-I standard deviation score (SDS) of -4.85 (quartiles -9.56 to -2.80). Of the 13 patients with APD and Cushing's disease, all were gonadotrophin and TSH-deficient, six were adrenocorticotropic hormone (ACTH)-deficient and six (46.1%) had cranial diabetes insipidus (CDI). Of the remaining nine patients with APD, total anterior pituitary hormone failure was present in all and CDI was present in two (22.2%)., Conclusions: The presence of APD indicates severe hypopituitarism in adults with HPA disease. It is universally associated with severe GHD. It is more common after surgery to the HP region. It has a low overall prevalence except in patients surgically treated for Cushing's disease.

Galanin is a biologically active 29 amino acid peptide, widely distributed in the central and peripheral nervous system, and most abundantly in the hypothalamus where it may serve in the regulation of anterior pituitary hormones. We herein report that mice carrying the rat preprogalanin cDNA specifically targeted to the somatomammotroph cell lineage, under the control of the rat GH promoter, over-express and over-secrete galanin. Galanin peptide is localised within the GH and prolactin secretory granules. GH and prolactin release is increased as well, predominantly in males, while older transgenic animals develop pituitary hyperplasia and adenoma. In both male and female transgenic mice there is a significant increase in serum galanin (P<0.00003 and P<0.001 respectively) and prolactin (P<0.002 and P<0.05 respectively) levels, while only in male transgenic mice is there a significant increase in the serum levels of GH. Furthermore, in male transgenic mice serum prolactin levels are significantly correlated with the serum galanin levels (P<0.03). We conclude that galanin plays a key role in the process of pituitary hyperplasia, acting as a growth factor to promote pituitary cell proliferation, and participates in pituitary adenoma formation not necessarily dependent on oestrogens. Targeted over-expression and over-secretion of galanin in the somatomammotroph cell lineage stimulates predominantly hyperprolactinaemia in an oestrogen-independent manner.

Ghrelin is a novel GH (growth hormone)-releasing peptide isolated from the stomach. The cardiovascular and hormonal effects of the subcutaneous administration of ghrelin in humans remain unknown. Six healthy volunteers each received subcutaneous administration of three doses of ghrelin (1, 5 or 10 microg/kg) and placebo; the order of administration was randomized, and separate doses were given at least 24 h apart. The serum GH level dose-dependently increased from 0.5 +/- 0.4 to 3.6 +/- 2.1 ng/ml (1 microg/kg ghrelin; P=0.99 compared with baseline), 27.1 +/- 12.0 ng/ml (5 microg/kg; P<0.01 compared with baseline) and 45.4 +/- 12.8 ng/ml (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. Subcutaneous administration of ghrelin did not significantly alter circulating levels of corticotropin, cortisol, insulin-like growth factor-1, noradrenaline or adrenaline, although 10 microg/kg ghrelin slightly increased the prolactin level. No significant changes in heart rate or mean arterial pressure were observed. In contrast, the left ventricular ejection fraction, as assessed by echocardiography, increased dose-dependently from 63.5 +/- 0.6% to 65.1 +/- 0.9% (1 microg/kg ghrelin; P=0.97 compared with baseline), 69.6 +/- 1.3% (5 microg/kg; P<0.01 compared with baseline) and 71.5 +/- 0.9% (10 microg/kg; P<0.01 compared with baseline) 30 min after ghrelin administration. These haemodynamic and hormonal changes were still apparent 60 min after ghrelin injection. In conclusion, subcutaneous administration of ghrelin dose-dependently induced relatively specific GH release and enhanced cardiac performance in humans.

We report the development of a sensitive, and specific, competitive, antigen-capture enzyme-linked immunosorbent assay for the measurement of channel catfish (Ictalurus punctatus) growth hormone (cfGH). The detection limit of the assay (90% binding) was 2.0ng/ml and the ED(50) value (standard curve range 150-0.59 ng/ml) was 67.3 ng/ml. Recovery of cfGH-spiked plasma samples was determined to be 102%. Dose-response inhibition curves using serially diluted pituitary homogenates and plasma samples consistently showed parallelism with the standard curves using purified cfGH. The GH antibody (rabbit anti-catfish GH) specificity was demonstrated in competitive binding curves employing heterologous hormones and purified channel catfish prolactin (cfPRL). These studies show that there was no significant (0.006%) binding of cfPRL (competitive inhibition of cfGH binding), or heterologous hormones, within the working range of the assay. To physiologically validate the assay, catfish were injected (100 microg/g body weight, 3 injections every 5 days) with either bovine GHRH(1-29)-amide or the synthetic hexapeptide GHRP-2 (KP-102: D-Ala-D-beta-Nal-Ala-Trp-D-Phe-Lys-NH(2)) suspended in corn oil. Following the last injection, half of the animals were sampled for plasma and the remaining transferred from fresh water (FW) to 12 ppt seawater (BW: brackish water). Twenty-four hours after transfer to BW, animals were again sampled for plasma. Plasma GH levels were significantly (p<0.001) elevated in all the BW groups (control, KP-102, and bGHRH), compared with the FW (fresh water) groups. In addition, plasma GH levels were significantly (p<0.001) elevated by treatment with either of the GH secretogogues, KP-102 or bGHRH. Our findings demonstrate that two regulatory mechanisms of GH elevation, one which is seen in euryhaline teleosts (salinity-induced GH levels) and another, which has been recently described in teleosts (GHRP-induced GH levels), are present in the stenohaline channel catfish.

Ghrelin a novel peptide consisting of 28 amino acids was first identified in the stomach in 1999. It is mainly produced in endocrine cells of the human gastric mucosa, but it was also found in several other tissues e. g. in the pituitary, the hypothalamus and the pancreas. The functional receptor belongs to the family of the 7-transmembrane G-protein receptors and is predominantly detected in the pituitary and at lower levels in hypothalamic nuclei, the stomach, heart, lungs, kidneys, gut, the adipose and many other tissues. According to the widespread distribution of the peptide and its receptor, ghrelin has multiple biological effects: it stimulates the release of growth hormone in the pituitary and induces a rise in the serum concentration of ACTH, cortisol, catecholamines and prolactin. Ghrelin causes an increase of food intake and body weight by stimulating the production of neuropeptide Y (NPY) and agouti-related protein (AGP) in the nucleus arcuatus. It further leads to elevated concentrations of plasma glucose. A physiological antagonism between ghrelin and GLP-1 in the hypothalamic regulation of appetite is being discussed. The basic serum level of ghrelin depends on the state of nutrition and is negatively correlated with the body-mass-index. It shows a certain pattern of variation before and after food intake with a preprandial increase and a postprandial decrease. Ghrelin modulates gastric acid secretion and the gastrointestinal motility via vagal cholinergic pathways. The discovery of ghrelin definitely contributes to the understanding of the growth-hormone secretion and of the regulation of appetite and food intake.