Search

We have studied in vivo induction of serum prolactin (PRL) levels in four females and one male, and regulation of PRL in the menstrual cycle in three females all with hyperprolactinemia with large amounts (72–92%) of bigbig PRL (MW 150–170 kD). Metoclopramide (MTC) iv induced a 4–29-fold increase in little PRL (25 kD PRL) at 30 min, while the increase in 150–170 kD PRL was 1.1–2.2-fold. The maximal response in 150–170 kD PRL was seen after 2–6 h, and the decrease after the maximal PRL values for 150–170 kD PRL was delayed compared to the decrease in 25 kD PRL. The different kinetics for 25 kD PRL and 150–170 kD PRL was responsible for the prolonged increase in total PRL seen in the subjects with large amounts of 150–170 kD PRL compared to the controls. The percentage of 1 50–170 kD PRL decreased to 29–60% at 30 min and returned to unstimulated values after 6–24 h. In contrast, prolonged stimulation of PRL secretion, as in the luteal phase, did not change the percentage of 150–170 kD PRL. In a male subject secreting large amounts of 1 50–170 kD PRL the increase in PRL after MTC was less, while the temporal changes in the 25 kD PRL levels were almost the same as in the females.

The responses of serum prolactin (Prl) to metoclopramide and LH and FSH to GnRH were studied simultaneously in 9 boys with hypogonadotrophic hypogonadism (HH), 7 boys with constitutional delay of puberty (D) and 15 controls. Metoclopramide increased the Prl levels in all groups. The boys with HH had lower Prl responses than the controls, whereas the boys with D had similar responses to the controls. Of the 9 boys with HH, 8 had subnormal Prl responses, 3 subnormal LH and none subnormal FSH. A metoclopramide test is clearly more sensitive than a GnRH test in differentiating HH and D and appears to make the differentiation between these two conditions clearer.

In order to determine whether or not the pituitary responsiveness to thyrotrophin-releasing hormone (TRH) changes during the nyctohemeral cycle, 10 healthy regularly cycling women were given 200 μg of TRH at 02.00 h, 10.00 h and 18.00 h with at least a 32 h interval between each test. Serum prolactin (Prl) and thyrotrophin (TSH) in 7 of the 10 women were measured serially before and after TRH administration. The mean basal Prl levels were significantly higher (P < 0.01) at 02.00 h than at 10.00 h and 18.00 h. The mean basal TSH levels were higher, although not significantly, at 02.00 h than at 10.00 h and 18.00 h. Although a higher TSH release occurred at 02.00 h than at 10.00 h and 18.00 h, the mean serum TSH and Prl peak responses to TRH were statistically similar in the three groups of tests. The integrated changes scores, calculated as the difference between the average post-TRH hormonal release and the average baseline levels, although higher in the 18.00 h test for Prl and the 02.00 h test for TSH, were not statistically different among the three tests.

The clinical significance of hyperprolactinaemia in uraemic patients is uncertain and discrepancies between immunoactivity and biological activity of serum hPRL have been reported. We have modified the Nb2 cell bioassay to improve specificity for hPRL and used this assay to measure hPRL bioactivity in sera from 26 uraemic patients and 40 control subjects. Seventeen patients were receiving regular haemodialysis and 9 continuous ambulatory peritoneal dialysis. Levels of hPRL bioactivity were compared with hPRL immunoactivity measured by RIA (PRL-RIA) and by immunoradiometric assay (PRL-IRMA). Serum hPRL levels measured by all three assays were significantly elevated in uraemic patients compared with control subjects (P< 0.001). The immunoradiometric method gave significantly lower results than RIA in control subjects but not in uraemic patients (P< 0.05). There was no significant difference in mean ratio of hPRL bioactivity to PRL-RIA between patients and control subjects (1.18 ± 0.05 vs 1.11 ± 0.03, mean ± sem). The ratio of hPRL bioactivity to PRL-IRMA was slightly decreased in uraemic patients compared with controls (P = 0.05). Serum hPRL bioactivity was closely correlated with immunoactivity in both immunoassays (r ≥ 0.96) in patients and controls. These results confirm that elevated serum hPRL levels in uraemic patients represent biologically active hormone which may contribute to hypogonadism.

The effect of hyperprolactinaemia on the hypothalamo-pituitary axis was assessed by iv injection of 100 μg luteinizing hormone releasing hormone (LRH) in 7 women with prolactinoma before and 3 months after normalization of the Prl level by transsphenoidal surgery. A dose of 20 mg of conjugated oestrogen (Premarin®) was also injected iv into patients with prolactinoma before and 4 months after surgery, and the serum LH levels were determined serially for 120 h after the injection. Surgical treatment caused significant reduction of the mean (± se) serum prolactin (Prl) level from 123.3 ± 7.8 to 19.4 ± 5.6 ng/ml. But the differences in the basal levels of LH (11.3 ± 2.2 to 8.6 ± 1.5 mIU/ml), FSH (8.3 ± 2.4 to 10.6 ± 3.7 mIU/ml) and oestradiol (26.6 ± 8.6 to 37.5 ± 5.5 pg/ml) before and 4 months after surgery were not significant. An exaggerated LH response to LRH in untreated prolactinoma patients was also observed after surgical treatment. After surgical treatment, patients showed LH release with a peak between 48 and 72 h after the injection of Premarin, whereas before treatment they did not show any LH discharge. The mean percent increase in LH between 48 and 72 h was also significantly higher after operation than before operation. These results suggest that the hyperprolactinaemia in prolactinoma patients may cause an impaired positive feedback effect of oestrogen on LH release and that this derangement can be reversed by reduction of the Prl level by adenomectomy.

To evaluate further the pharmacological properties of dihydroergocristine in vivo, this drug (6 mg) or a placebo were administered orally on separate days to 11 healthy controls, 11 patients with adenomatous (n = 4) or idiopathic hyperprolactinaemia (n = 7), and 5 acromegalics with raised serum prolactin levels; serum prolactin (Prl) and growth hormone (GH) were measured at hourly intervals for 6 h. Dihydroergocristine induced a significant Prl decrease versus placebo in hyperprolactinaemics and acromegalics, but had no effect in healthy subjects. GH levels did not change in normals and hyperprolactinaemics, but decreased significantly in acromegalics. The Prl decrease induced by dihydroergocristine was significantly lower than that induced by l-dopa (500 mg po) in 9 hyperprolactinaemics so tested. Nomifensine (200 mg po) administered to 7 hyperprolactinaemics had no effect. Similarly, the GH decrease induced by the drug in acromegalics was significantly lower than that exerted by l-dopa, while nomifensine had no effect. Five hyperprolactinaemic patients were also given 12–18 mg dihydroergocristine daily for 3 months. There was evidence of partial or total Prl suppression and resumption of menses in all patients. These data indicate that dihydroergocristine is a relatively weak dopamine agonist at pituitary level and that oral doses, insufficient to exert Prl-lowering activity in normal subjects, are able to inhibit Prl and GH release in hyperprolactinaemics and dopamine-responsive acromegalics. These findings further support the existence of a 'denervation' supersensitivity to dopamine in these conditions, in which dopamine deficiency at pituitary level has been suggested on the basis of other experiments.

Serum samples were obtained from 7 subjects (6 men and 1 woman) in the morning (09.00 h) and in the afternoon (15.00 h) of each week for a period of 13 months and assayed for prolactin by RIA. In addition, 4 female monkeys were sampled once weekly in the afternoon for approximately two years. The data were analyzed for cyclicity by power spectrum analysis. In both species a serum prolactin circannual cycle was not obvious. In most subjects statstically significant (P

In 8 patients with diabetic ketoacidosis, serum prolactin was measured and found to be elevated (24.8 ± 10.2 ng/ml, mean ± sem). After correction of the ketoacidosis, the prolactin level decreased to 10.9 ± 6.4 ng/ml (normal range men 4.9 ± 0.8, women 5.1 ± 1.6 ng/ml). The scatter of prolactin values was wide. A study of the correlation between the serum prolactin values and chemical parameters that are altered in diabetic ketoacidosis was therefore undertaken. Serum prolactin values did not correlate well with the serum bicarbonate concentration or serum osmolality. However, a significant negative correlation between log serum prolactin concentration and serum sodium concentration was demonstrated (r=−0.61, P It is suggested that serum prolactin may possibly participate in sodium retention in man as has been demonstrated in studies on animals.

Plasma concentrations of 1,25-dihydroxyvitamin D (1,25–(OH)2D), serum prolactin and serum parathyroid hormone (PTH) were followed during pregnancy and lactation in 16 women. High 1,25–(OH)2D was demonstrated in human pregnancy and lactation. A causative relationship between 1,25–(OH)2D and prolactin is discussed and a possible explanation of the mechanism of the augmented calcium absorption in human pregnancy and lactation is suggested.

Pentobarbital lengthens the estrous cycle when injected on diestrus 1 afternoon in the 4-day cyclic female rat. The present study was undertaken to elucidate the mechanisms involved. Bromocriptine (2.5 mg/kg sc) given 30 min before pentobarbital (30 mg/kg ip) prevented the effects of pentobarbital on both cycle lengthening and progesterone levels in diestrus 2. Serum prolactin concentrations rose 10 min after pentobarbital injection, peaked at 30 min, and returned to control values after 60 min. Our results suggest that pentobarbital-induced cycle lengthening is due to a high progesterone production on diestrus 2 morning related to the luteotropic action of prolactin.

Ten young healthy normal-weight males were studied in four test situations designed to elucidate the relative role of body temperature increase vs that of exercise per se for pituitary hormone release. Tympanic temperature was recorded continuously during the tests. Elevation of body temperature at rest induced by external heating resulted in parallel changes in serum prolactin (Prl), also found when temperature spontaneously returned towards normal. In contrast, temperature elevation of the same magnitude through exercise (450 kpm/min for 40 min) induced no change in Prl secretion. It is concluded that increase in core temperature is a stimulus of Prl secretion and suggested that exercise apparently inhibits the stimulatory effect.

The effect of pyridoxine (B6) on galactorrhoea, amenorrhoea, and the galactorrhoea-amenorrhoea syndrome was studied in 22 patients. No consistent change in serum prolactin concentration and no resumption of ovulation were seen during 3 months B6 therapy. Inappropriate lactation ceased in 3 of 10 patients with galactorrhoea alone, and menses were restored in 2 of 9 patients with the galactorrhoea-amenorrhoea syndrome while on B6 therapy. Our results suggest that B6 is not generally effective in the treatment of galactorrhoea-amenorrhoea syndromes.

Histidyl-proline-diketopiperazine (DKP) - a stable degradation product of TRH - has been shown to selectively inhibit prolactin secretion in vitro in rat pituitary tissue. In this study the effects of DKP on serum prolactin in intact and anaesthetized male rhesus monkeys and on TRH-stimulated prolactin levels have been investigated. In conscious monkeys 400 μg DKP significantly suppressed prolactin levels by 27%, and under ketamine anaesthesia, serum prolactin was suppressed in a dose-dependent manner by 150 and 400 μg DKP. The maximum prolactin response and the cumulative response to TRH (20 μg) was significantly and specifically inhibited by 400 μg DKP, while the lower dose was without effect. TSH levels were not affected by DKP in any instance. Hence DKP can specifically inhibit prolactin release in the rhesus monkey, and may be discussed as a possible regulatory factor in prolactin secretion.

In order to evaluate the function of the hypothalamic-pituitary-prolactin axis in "adolescent gynaecomastia" (AG), sulpiride was administered to 7 normal boys and 7 boys with AG. The maximum increase in serum prolactin (PRL) above the mean baseline level (Δmax) was used as index of response. The sulpiride induced a greater PRL release in boys with gynaecomastia than in the controls. Our data indicate that boys with gynaecomastia may have a greater pituitary prolactin pool. The results also illustrate the usefulness of specific neurotrophic agents such as sulpiride as important tools for evaluating the function of the hypothalamic-pituitary-PRL axis.

Specific binding sites for prolactin (PRL) and gonadotrophins on ventral and dorsolateral prostate as well as on Leydig cells and tubules of testes of rats at different ages were examined. The binding sites for PRL were found in greatest number in ventral prostate and in Leydig cells. LH binding sites were also more numerous than FSH binding sites in the latter. FSH sites were greater than LH sites in tubular preparations obtained from the testis. Specific binding (SB) of PRL in the Leydig cells reached a maximum at 45 days (4%) and in the case of LH a maximum of 12% was obtained at 70 days. In both preparations SB of FSH exhibited a plateau between 20 and 40 days (11%) followed by a gradual decline to 6% at 100 days. Following 20 days of treatment with Bromocriptin beginning at 20 days serum PRL was suppressed and SB of LH to the Leydig cells was significantly decreased, whereas SB of PRL and FSH was unaffected. These studies suggest that despite decreases in serum PRL, the number of PRL and FSH receptors remain unaltered. On the contrary, LH receptors in the rat testis are modulated by changes in serum PRL.

Five mg of bromocriptine was administered for 3 weeks to 8 hyperprolactinaemic women with galactorrhoea-amernorrhoea, in whom the response of serum luteinizing hormone (LH) and follicle-stimulating hormone (FSH) to 100 μg of iv LH-releasing hormone (LH-RH) had been evaluated. Twenty mg of conjugated oestrogen (Premarin®) was injected iv any day between the 10th and 12th day from the initiation of the treatment, and serum LH levels were serially determined for 120 h. Hyperresponse of LH with normal FSH response to LH-RH was observed in most patients. Bromocriptine treatment for 10 to 12 days significantly suppressed mean (± se) serum prolactin (PRL) levels from 65.1 ± 23.0 to 10.4 ± 2.0 ng/ml, while LH (12.6 ± 2.1 to 24.8 ± 5.9 mIU/ml) and oestradiol (40.1 ± 7.6 to 111.4 ± 20.8 pg/ml) levels increased significantly. Patients on bromocriptine treatment showed LH release with a peak at 48 h after the injection of Premarin. The mean per cent increases in LH were significantly higher than those in untreated patients with galactorrhoea-amenorrhoea between 32 and 96 h after the injection. The present results seem to suggest that the restoration of LH-releasing response to oestrogen following suppression of PRL by bromocriptine may play an important role in induction of ovulation in hyperprolactinaemic patients with galactorrhoea-amenorrhoea.

Serum prolactin levels and milk yield were studied in 27 puerperae with excessive milk production (polygalactia) and compared with 30 normally lactating puerperae. In order to normalize polygalactia, 14 of these women were treated with 2.5 mg bromocriptine per day for 3 days starting on post-partum day 5, 13 women received placebo. Milk flow in polygalactic women started significantly earlier than in puerperae with normal milk yield and developed mean milk volumes of 816 g per day on post-partum day 4. Serum prolactin levels did not differ from levels of puerperae with normal milk yield. There was no correlation between serum prolactin and milk yield. Bromocriptine treatment resulted in a sharp but reversible decline of serum prolactin levels followed by a significant reduction of milk production. Bromocriptine could not be detected in milk specimens, while serum levels showed significant amounts. In placebo treated women prolactin levels and milk yield remained unaffected. These data indicate that serum prolactin concentrations of puerperae with polygalactia are within the normal post-partum range. Short term prolactin suppression by bromocriptine can reduce milk yield, without complete ablactation.

In 18 female patients affected by advanced breast cancer, the serum prolactin (PRL) levels have been determined under basal conditions and after the administration of analgesic opiates such as methadone and pentazocine. A significant increase of prolactin serum values was found after the use of both drugs. This finding is considered to be of clinical importance.

Female Sprague-Dawley derived rats were either sham-operated or adrenalectomized at 20 days of age. Treatment of separate groups of rats with progesterone, corticosterone or prolactin was started at 21 days of age, and was continued until the day of vaginal opening. Similarly treated rats were decapitated at 25, 29 and 33 days of age and at the day of vaginal opening and the sera were collected from each animal and assayed for prolactin, LH and FSH. All rats were decapitated between 4–6 p. m. Adrenalectomy, as previously reported, significantly delayed the day of vaginal opening. Prolactin treatment advanced the day of vaginal opening in intact rats and it restored the day of vaginal opening in adrenalectomized rats to that of intact control rats. Progesterone treatment always delayed the day of vaginal opening in intact rats. It caused an even greater delay in vaginal opening than adrenalectomy alone. Corticosterone treatment, on the other hand, was able to reverse the effect of adrenalectomy but had no effect on vaginal opening in intact rats. In intact rats serum prolactin levels rose steadily until the day of vaginal opening. Adrenalectomized and intact rats treated with progesterone had significantly decreased serum prolactin levels. However, in adrenalectomized corticosterone treated rats serum prolactin levels were significantly increased at all ages measured when compared to the untreated rats. The FSH and LH levels showed no significant changes during any of these experimental procedures. Approximately 50 % of the rats showed LH peaks on the day of vaginal opening as well as an increase in FSH. The data indicate a prolactin-adrenal interaction for the timing of the onset of puberty in immature rats, assuming that the day of vaginal opening in association with increased gonadotrophin levels is an indicator for the occurrence of puberty.