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Purpose: It is unclear whether the age-related decline in the somatotropic axis stems from a reduced growth hormone (GH) production in the pituitary gland, or from a peripheral origin akin to an acquired GH resistance. With the help of a GHRH/arginine test, high-aged multimorbid hospitalized patients with IGF-I deficiency are to be tested to determine whether there is primarily a pituitary GH deficiency in the sense of a somatopause. Methods: Seventeen multimorbid patients (eleven men and six women) with a mean age of 82 years, with IGF-I concentrations below two standard deviations of 30-year-old men and women were identified. Patients suffered from a variety of common age-related stable diseases including coronary artery disease, chronic liver or kidney disease, chronic heart failure as well as acute conditions e.g., urosepsis or endocarditis. To assess the somatotropic axis they underwent a GHRH/arginine test. Results were evaluated using descriptive statistics. Results: In average, the peak concentration of GH after stimulation was 14.8 µg/L with a range from 2.76 to 47.4 µg/L. Taking into account both, gender and BMI (with a mean of 26.5 kg/m²) for each participant, the pituitary gland was adequately stimulated in 16 out of the 17 patients. No patient reported common side effects related to the GHRH/arginine test. Conclusion: The somatotroph pituitary gland retains its secretory capacity in the advanced aged. Therefore, age does not seem to be the driving pacemaker for the functional decline of the somatotropic axis within the aged population. [ABSTRACT FROM AUTHOR]

Abstract Background The insulin-like growth factor (IGF-I) and growth hormone (GH) genes have been identified as major regulators of milk yield and composition, and reproductive performance in cattle. Genetic variations/polymorphism in these genes have been found to influence milk production, yield and quality. This investigation aimed to explore the association between IGF-I and GH polymorphisms and milk yield and composition, and reproductive performance in a herd consisting of 1000 Holstein–Friesian (HF) dairy cattle from El-Alamia farm. The experimental animals were 76 ± 7.25 months in age, with an average live weight of 750 ± 50.49 kg, and raised under the same conditions of feeding and weather. The studied animals were divided into three categories; high producers (n = 280), medium producers (n = 318) and low producers (n = 402). Results The digestion of 249 bp for IGF-I-SnaBI using the Restriction-fragment-length-polymorphism (RFLP) technique yielded two alleles; T (0.59) and C (0.41) and three genotypes; TT (0.52), TC (0.39) and CC (0.09) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the IGF-I gene revealed polymorphism in position 472 (C > T). Nucleotide sequencing of the amplified fragment of the IGF-I gene of different genotypes was done and submitted to the NCBI GenBank with Accession no. MH156812.1 and MH156811.1. While the digestion of 432 bp for GH-AluI using the RFLP technique yielded two alleles; A (0.81) and G (0.19) and two genotypes; AA (0.77) and AG (0.23) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the GH gene revealed polymorphism in the position 1758 C > G and in turn led to changes in amino acid sequence as Alanine for (A) compared to Glycine for (G). Nucleotide sequencing of the amplified fragment of the GH gene was done and submitted to the NCBI GenBank with Accession no. MH156810.1. The results of this study demonstrate the effects of variants of the GH-IGF-I somatotrophic axis on milk production and composition traits in commercial HF cattle. The greatest values of milk yield and reproductive performance were observed on IGF-I-SnaBI-TC and GH-AluI-AG genotypes. While the greatest % fat and % protein values were observed on IGF-I-SnaBI-CC and GH-AluI-AA genotyped individuals. Conclusion The genetic variation of the studied genes can be utilized in selecting animals with superior milk yield, composition and reproductive performance in Holstein–Friesian Dairy Cattle under subtropical conditions.

Background: The insulin-like growth factor (IGF-I) and growth hormone (GH) genes have been identified as major regulators of milk yield and composition, and reproductive performance in cattle. Genetic variations/polymorphism in these genes have been found to influence milk production, yield and quality. This investigation aimed to explore the association between IGF-I and GH polymorphisms and milk yield and composition, and reproductive performance in a herd consisting of 1000 Holstein–Friesian (HF) dairy cattle from El-Alamia farm. The experimental animals were 76 ± 7.25 months in age, with an average live weight of 750 ± 50.49 kg, and raised under the same conditions of feeding and weather. The studied animals were divided into three categories; high producers (n = 280), medium producers (n = 318) and low producers (n = 402). Results: The digestion of 249 bp for IGF-I-SnaBI using the Restriction-fragment-length-polymorphism (RFLP) technique yielded two alleles; T (0.59) and C (0.41) and three genotypes; TT (0.52), TC (0.39) and CC (0.09) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the IGF-I gene revealed polymorphism in position 472 (C > T). Nucleotide sequencing of the amplified fragment of the IGF-I gene of different genotypes was done and submitted to the NCBI GenBank with Accession no. MH156812.1 and MH156811.1. While the digestion of 432 bp for GH-AluI using the RFLP technique yielded two alleles; A (0.81) and G (0.19) and two genotypes; AA (0.77) and AG (0.23) and this agrees with the results of DNA/gene sequencing technique. The sequencing analysis of the GH gene revealed polymorphism in the position 1758 C > G and in turn led to changes in amino acid sequence as Alanine for (A) compared to Glycine for (G). Nucleotide sequencing of the amplified fragment of the GH gene was done and submitted to the NCBI GenBank with Accession no. MH156810.1. The results of this study demonstrate the effects of variants of the GH-IGF-I somatotrophic axis on milk production and composition traits in commercial HF cattle. The greatest values of milk yield and reproductive performance were observed on IGF-I-SnaBI-TC and GH-AluI-AG genotypes. While the greatest % fat and % protein values were observed on IGF-I-SnaBI-CC and GH-AluI-AA genotyped individuals. Conclusion: The genetic variation of the studied genes can be utilized in selecting animals with superior milk yield, composition and reproductive performance in Holstein–Friesian Dairy Cattle under subtropical conditions. [ABSTRACT FROM AUTHOR]

Abstract Background The somatotrophic axis, including hypothalamic growth hormone (GH)-releasing hormone (GHRH), pituitary GH and circulating IGF-I, is critical for body size. However, the local production of GH/IGF-I (and IGF-II) and other peptides is relevant for other body functions, such as vascular, brain, and retinal function. The consequences of GH deficiency (GHD) on the retinal structure are still unclear, possibly reflecting the heterogeneity of patients and the different types of assessment in previous publications. Our purpose was to assess quantitative measures of the vascular and neural components of the retina in subjects with severe congenital isolated GHD (IGHD). Methods A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, optical coherence tomography (OCT) and OCT angiography (OCTA) were performed. Results OCT revealed no difference in the areas of the nerve fiber layer average, nor in the areas of superior, inferior, or nasal quadrants, between the two groups. However, areas of the temporal quadrant (p = 0.041), the optical disc (p = 0.042), the cup (p

Objective: Active acromegaly is subject to sex differences in growth hormone (GH) and Insulin like growth factor 1 (IGF‐I) patterns as well as clinical features but whether this also pertains to controlled disease is unclear. Design: In a cross‐sectional, multi‐centre study, 84 patients with acromegaly (F = 43, M = 41), who were considered controlled after surgery alone (n = 23) or during continued somatostatin receptor ligand (SRL) treatment (n = 61), were examined. Methods: Serum concentrations of GH, insulin, glucose and free fatty acid (FFA) were measured during an oral glucose tolerance test (OGTT) together with baseline serum IGF‐I and completion of two HR‐Qol questionnaires (acromegaly quality of life questionnaire [AcroQol] and Patient‐assessed Acromegaly Symptom Questionnaire [PASQ]). Results: The mean age at the time of the study was 57 (±1.1) years and the majority of females (were postmenopausal. Females had significantly higher fasting GH but comparable IGF‐I standard deviation scores (SDS). Using fasting GH < 1.0 µg/L as cut off, disease control was less prevalent in females (F: 56% vs. M: 83%, p =.007) whereas a comparable figure was observed using IGF‐I SDS < 2 (F:79% vs. M:76%, p =.71). Compared with males, female patients showed impaired AcroQol physical score (p =.05), higher fasting FFA (p =.03) and insulin concentrations during the OGTT (p =.04). Conclusion: In patients with acromegaly considered controlled, postmenopausal females exhibited higher GH levels than males despite comparable IGF‐I levels, which also translated into impaired metabolic health and well‐being. Our findings point to the relevance of including GH measurements in the assessment of disease control and suggest that disease‐specific sex differences prevail after treatment. [ABSTRACT FROM AUTHOR]

Introduction: Treatment of acromegaly resistant to first generation somatostatin analogues (first gen-SSA) is often difficult. We aimed to investigate the role of partial response and resistance to first gen-SSA in the choice of second line treatments and their outcomes. Patients and methods: A retrospective and multicenter study was conducted on 100 SSA-resistant acromegaly patients and treated with Pasireotide Lar (Pasi-Lar), Peg-V in monotherapy (m-Peg-V) or in combination with first gen-SSA (c-Peg-V). Results: Thirty-three patients (33%) were treated with m-Peg-V, 36 (36%) with c-Peg-V and 31 with Pasi-Lar (31%). According to logistic regression, m-Peg-V was chosen in older patients (p = 0.01) and with not-invasive adenomas (p = 0.009), c-Peg-V therapy in younger patients (p = 0.001), with invasive adenomas (p = 0.02), Pasi-Lar was in invasive adenomas (p = 0.01) and in patients partially responsive to first-gen SSA (p = 0.01). At the last follow-up, 68 patients (68%) reached the acromegaly control: 22 with m-Peg-V (32.4%), 23 with c-Peg-V (33.8%) and 23 with Pasi-Lar (33.8%). Patients non-responsive to c-Peg-V had higher IGF-I levels (median 3.2 x ULN, IQR: 1.6, p < 0.001) and required higher Peg-V dosage (median 30 mg/daily IQR: 10, p = 0.002) as compared to responsive patients (median IGF-I x ULN: 2.1 IQR: 1.4; median Peg-V dosage 20 mg/daily IQR: 10). All patients responsive to Pasi-Lar were partially responsive to first gen-SSAs (p = 0.02). Conclusion: Our data showed that c-Peg-V and Pasi-Lar are chosen for the treatment of invasive tumors. The partial response to first gen-SSA seems to be the main determinant for the choice of Pasi-Lar and positively predicts the treatment outcome. [ABSTRACT FROM AUTHOR]

Background: The somatotrophic axis, including hypothalamic growth hormone (GH)-releasing hormone (GHRH), pituitary GH and circulating IGF-I, is critical for body size. However, the local production of GH/IGF-I (and IGF-II) and other peptides is relevant for other body functions, such as vascular, brain, and retinal function. The consequences of GH deficiency (GHD) on the retinal structure are still unclear, possibly reflecting the heterogeneity of patients and the different types of assessment in previous publications. Our purpose was to assess quantitative measures of the vascular and neural components of the retina in subjects with severe congenital isolated GHD (IGHD). Methods: A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, optical coherence tomography (OCT) and OCT angiography (OCTA) were performed. Results: OCT revealed no difference in the areas of the nerve fiber layer average, nor in the areas of superior, inferior, or nasal quadrants, between the two groups. However, areas of the temporal quadrant (p = 0.041), the optical disc (p = 0.042), the cup (p < 0.0001), as well as the cup/disc ratio (p < 0.0001), were higher in IGHD subjects than controls. The rim area was smaller (p = 0.002), although still normal. In OCTA, there was no difference in the minimum foveal thickness, central fovea, foveal avascular zone, and retinal density in any assessed area. Conclusions: In conclusion, congenital IGHD does not affect quantitative measures of the vascular and neural retina, and it is associated with increased optical disc in this genetically homogeneous cohort. [ABSTRACT FROM AUTHOR]

Context: In patients with acromegaly on long-term treatment with long-acting somatostatin receptor ligands (SRLs), the time of blood collection for IGF-I measurement after injection is not well defined. Objective: We aimed to assess serum IGF-I dynamics and variability in SRL-treated patients compared with surgically cured patients and healthy controls. Methods: Thirty patients under SRLs considered controlled based on a normal previous IGF-I level, 10 patients cured by pituitary surgery, and 7 healthy subjects underwent 4 weekly IGF-I determinations. Results: In SRL-treated patients, the IGF-I SDS (mean ± SD) was higher just before injection (0.34 ± 0.66) than at Day 7 (−0.33 ± 0.61; P = 0.0041) and Day 14 (−0.23 ± 0.60; P = 0.047) after injection, but it did not significantly vary in cured patients and healthy controls. The IGF-I CV was higher in SRL-treated patients than in cured patients or healthy controls (14.4 ± 7.6% vs 7.9 ± 4.4% and 8.3 ± 3.2%, respectively; P < 0.05 for both). Among SRL-treated patients, IGF-I CV was higher in “nonoptimally controlled patients”—i.e., patients with at least one elevated IGF-I value out of 4 (n = 9) compared with “optimally controlled” patients for whom all 4 IGF-I SDS values were < 2.0 (21.3 ± 9.3 vs 11.6 ± 6.0%; P = 0.0019). The latter did not differ from surgically cured patients and healthy controls. The measurement at the farthest distance from the SRL injection was the most predictive of patients with nonoptimally controlled disease. Conclusion: In patients treated with long-acting SRLs, IGF-I sampling at the farthest distance from SRL injection is the most informative and best predictor of optimal disease control. [ABSTRACT FROM AUTHOR]

Background: No previous systematic review has quantitatively compared the effects of resistance training, endurance training, or concurrent training on hormonal adaptations in children and adolescents. Objective was to examine the effects of exercise training and training type on hormonal adaptations in children and adolescents. Methods: A systematic literature search was conducted in the following databases: PubMed, Web of Science, and EBSCO. Eligibility criteria were: population: healthy youth population sample (mean age < 18 years); intervention: resistance training, endurance training, or concurrent training (> 4 weeks duration); comparison: control group; outcome: pre- and post-levels of hormones and cytokines; and study design: randomized and non-randomized controlled trials. We used a random-effect model for the meta-analysis. The raw mean difference in hormones from baseline to post-intervention was presented alongside 95% confidence intervals (CI). Further, the certainty of evidence quality and the risk of bias were assessed. Results: A total of 3689 records were identified, of which 14 studies were eligible for inclusion. Most studies examined adolescents with fewer studies on children (age < 12 years, N = 5 studies) and females (N = 2 studies). Nine exercise training programs used endurance training, five studies used resistance training, and no eligible study used concurrent training. The meta-analysis showed no significant effect of exercise training on testosterone (MD = 0.84 nmol/L), cortisol (MD = − 17.4 nmol/L), or SHBG (MD = − 5.58 nmol/L). Subgroup analysis showed that resistance training significantly increased testosterone levels after training (MD = 3.42 nmol/L) which was not observed after endurance training (MD = − 0.01 nmol/L). No other outcome differed between training types. Exercise training resulted in small and non-significant changes in GH (MD = 0.48 ng/mL, p = 0.06) and IGF-I (MD = − 22.90 ng/mL, p = 0.07). GH response to endurance training may be age-dependent and evident in adolescents (MD = 0.59 ng/mL, p = 0.04) but not when children and adolescents are pooled (MD = 0.48 ng/mL, p = 0.06). Limited evidence exists to conclude on IL-6 and TNF-α effects of exercise training. Assessments of GRADE domains (risk of bias, consistency, directness, or precision of the findings) revealed serious weaknesses with most of the included outcomes (hormones and cytokines). Conclusions: This systematic review suggests that exercise training has small effects on hormonal concentrations in children and adolescents. Changes in testosterone concentrations with training are evident after resistance training but not endurance training. GH's response to training may be affected by maturation and evident in adolescents but not children. Further high-quality, robust training studies on the effect of resistance training, endurance training, and concurrent training are warranted to compare their training-specific effects. Registration: PROSPERO: CRD42021241130. [ABSTRACT FROM AUTHOR]

Growth hormone (GH) administration increases bone strength in rats, mainly through alterations of the dimensional proportions of vertebrae. However, similar knowledge is lacking in other clades. In order to pursue this, Atlantic salmon were fed diets with high or low vitamin C and E and administered a slow-release implant of bovine GH. While neither the diets or the GH treatment affected growth, GH reduced condition factor and carcass-somatic index, and increased the hepatosomatic and visceral-somatic indexes. GH had an impact on the dimensional proportions of the vertebrae and increased the relative dorso-ventral and lateral vertebra diameters. Moreover, GH decreased the mechanical strength of the vertebra, both with (modulus of elasticity, failure point) and without (stiffness) normalizing the mechanical data for the dimensions of the vertebrae. Diet did not impact on the vertebra morphometry or mechanical strength. RNA-seq of vertebra centra show that several genes associated with bone growth and remodelling were affected by GH, while there was an interactive effect between diet vitamin level and GH on several genes associated with lipid metabolism. The data may suggest that exogenous GH affects the bone cellular mechanisms of Atlantic salmon postsmolts in such a way that their vertebrae increase in diameter but not length, not disturbing growth in body length. The GH and diet effects on lipid metabolism associated genes indicate a complex regulation of the lipids stored inside the vertebral column by endocrine and nutritional factors. • GH decreased vertebra mechanical strength. • GH increased the diameter of the vertebra but not length. • GH affected bone growth and remodelling associated genes. • GH and diet vitamin C and E affected lipid metabolism associated genes. [ABSTRACT FROM AUTHOR]

This study aims to determine an effect between GH, IGF-I, and Pit-I gene polymorphisms and growth traits such as body weight, heart girth, body length, height at wither, and chest width in Saanen, Alpine, and Boer goat breeds. The polymorphism was identified using the PCR-RFLP technique. GH/ HaeIII gene polymorphism results identified two alleles (A and B) and two genotypes (AB and BB). A and B allele frequencies for Saanen, Alpine, and Boer goat breeds were found to be 0.438 and 0.562, 0.444 and 0.556, and 0.197 and 0.803, respectively. AB and BB genotype frequencies were found to be 0.876 and 0.124, 0.889 and 0.111, and 0.394 and 0.606, respectively. IGF-I/ HaeIII gene polymorphism results identified two alleles (A and B) and three genotypes (AB, BB, and AA). A and B allele frequencies for the Saanen, Alpine, and Boer breeds were found to be 0.191 and 0.809, 0.173 and 0.827, and 0.182 and 0.818, respectively. The AB, BB, and AA genotype frequencies were found to be 0.315, 0.652, and 0.033 for Saanen, 0.247, 0.704, and 0.049 for Alpine, and 0.242, 0.697, and 0.061 for Boer, respectively. Regarding Pit-I/ PstI gene polymorphism, T and C allele frequencies were determined as 0.921 and 0.079, 0.988 and 0.012, and 0.985 and 0.015 for Saanen, Alpine, and Boer breeds, respectively. TT and TC genotype frequencies were found to be 0.843 and 0.157, 0.975 and 0.025, and 0.970 and 0.030 in Saanen, Alpine, and Boer goats, respectively. An association was found between GH polymorphism and chest width in Saanen and Alpine goats and between body weight and heart girth in Boer goats. Additionally, an association was identified between IGF-I polymorphism and body weight in Alpine and chest width in Boer. There was also an association between Pit-I polymorphism and body weight in Alpine goats. • Gene Polymorphisms and Growth Traits in Goats: This study investigated the relationship between polymorphisms in the GH, IGF-I, and Pit-I genes and various growth traits (body weight, heart girth, body length, height at wither, and chest width) across Saanen, Alpine, and Boer goat breeds. The polymorphisms were detected using the PCR-RFLP technique. • GH Gene Polymorphism Findings: Analysis of the GH/ Hae III gene polymorphism revealed two alleles (A and B) and two genotypes (AB and BB). Notably, the A and B allele frequencies varied among Saanen (0.438 and 0.562), Alpine (0.444 and 0.556), and Boer (0.197 and 0.803) goats, indicating breed-specific genetic variations. • IGF-I Gene Polymorphism Outcomes: The study identified two alleles (A and B) and three genotypes (AB, BB, and AA) in the IGF-I/ Hae III gene polymorphism. The allele frequencies differed significantly across the breeds, showing a predominant presence of the B allele in Saanen, Alpine, and Boer goats. • Pit-I Gene Polymorphism Results: In examining the Pit-I/ Pst I gene polymorphism, T and C allele frequencies showed considerable breed-specific differences, with the TT and TC genotype frequencies indicating a strong presence of the T allele across all three goat breeds. • Associations Between Gene Polymorphisms and Growth Traits: The study found specific associations between gene polymorphisms and growth traits in goats. GH polymorphism was linked to chest width in Saanen and Alpine breeds, whereas IGF-I polymorphism correlated with body weight and chest width in Alpine and Boer goats, respectively. Moreover, Pit-I polymorphism was associated with body weight in Alpine goats, highlighting the genetic influence on growth characteristics across different breeds. [ABSTRACT FROM AUTHOR]

Insulin-like growth factor-I (IGF-I) regulates cell growth, survival, and differentiation by acting on the IGF-I receptor, (IGF-IR)-a tyrosine kinase receptor, which elicits diverse intracellular signaling responses. All skeletal cells express IGF-I and IGF-IR. Recent studies using tissue/cell-specific gene knockout mouse models and cell culture techniques have clearly demonstrated that locally produced IGF-I is more critical than the systemic IGF-I in supporting embryonic and postnatal skeletal development and bone remodeling. Local IGF-I/IGF-IR signaling promotes the growth, survival and differentiation of chondrocytes and osteoblasts, directly and indirectly, by altering other autocrine/paracrine signaling pathways in cartilage and bone, and by enhancing interactions among these skeletal cells through hormonal and physical means. Moreover, local IGF-I/IGF-IR signaling is critical for the anabolic bone actions of growth hormone and parathyroid hormone. Herein, we review evidence supporting the actions of local IGF-I/IGF-IR in the above aspects of skeletal development and remodeling.

IntroductionIn acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them.Materials and MethodsIt was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis.ResultsThe study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20–78) and 46 for men (range 24–76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent.ConclusionsIn our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups.

Purpose: Several interactions exist between the GH/IGF axis and the immune system, including effects on innate immunity and humoral and cellular response. Acquired GH deficiency (GHD) has been recently proposed as a risk factor for severity of COVID-19 infections. However, acquired GHD is often associated to other factors, including pituitary tumors, surgery, radiotherapy, and additional pituitary hormones deficits and their replacements, which, together, may hinder an accurate analysis of the relationship between GHD and COVID-19. Therefore, we decided to assess the seroprevalence of SARS-CoV-2 antibodies and the frequency of symptomatic cases of COVID-19 in adults subjects with untreated isolated GHD (IGHD) due to a homozygous null mutation in the GHRH receptor gene. Methods: A cross-sectional study was carried out in 27 adult IGHD subjects and 27 age- and gender-matched local controls. Interview, physical examination, bio-impedance, hematological and SARS-CoV-2 IgM and IgG antibodies were analyzed. Results: There was no difference in the prevalence of positivity of anti-SARS-CoV-2 IgM and IgG antibodies between the two groups. Conversely, no IGHD individual had a previous clinical diagnosis of COVID-19 infection, while 6 control subjects did (p = 0.023). Conclusion: The production of anti-SARS-CoV-2 antibodies was similar between IGHD subjects due to a GHRH receptor gene mutation and controls, but the evolution to symptomatic stages of the infection and the frequency of confirmed cases was lower in IGHD subjects than in GH sufficient individuals. [ABSTRACT FROM AUTHOR]

Objective: Data on sex differences in acromegaly at the time of diagnosis vary considerably between studies. Design: A nationwide cohort study including all incident cases of acromegaly (1978–2010, n = 596) and a meta‐analysis on sex differences in active acromegaly (40 studies) were performed. Method: Sex‐dependent differences in prevalence, age at diagnosis, diagnostic delay, pituitary adenoma size, insulin‐like growth factor 1 (IGF‐I) and growth hormone (GH) concentrations were estimated. Results: The cohort study identified a balanced gender distribution (49.6% females) and a comparable age (years) at diagnosis (48.2 CI95% 46.5–49.8 (males) vs. 47.2 CI95% 45.5–48.9 (females), p = 0.4). The incidence rate significantly increased during the study period (R2 = 0.42, p < 0.01) and the gender ratio (F/M) changed from female predominance to an even ratio (SR: 1.4 vs. 0.9, p = 0.03). IGF‐ISDS was significantly lower in females compared to males, whereas neither nadir GH nor pituitary adenoma size differed between males and females. In the meta‐analysis, the weighted percentage female was 53.3% (CI95% 51.5–55.2) with considerable heterogeneity (I2 = 85%) among the studies. The mean age difference at diagnosis between genders was 3.1 years (CI95% 1.9–4.4), and the diagnostic delay was longer in females by 0.9 years (CI95% −0.4 to 2.1). Serum IGF‐I levels were significantly lower in female patients, whereas nadir GH, and pituitary adenoma size were comparable. Conclusion: There are only a minor sex differences in the epidemiology of acromegaly at the time of diagnosis except that female patients are slightly older and exhibit lower IGF‐I concentrations and a longer diagnostic delay. [ABSTRACT FROM AUTHOR]

Introduction: In acromegaly, chronic exposure to impaired GH and IGF-I levels leads to the development of typical acromegaly symptoms, and multiple systemic complications as cardiovascular, metabolic, respiratory, endocrine, and bone disorders. Acromegaly comorbidities contribute to decreased life quality and premature mortality. The aim of our study was to assess the frequency of acromegaly complications and to evaluate diagnostic methods performed toward recognition of them. Materials and Methods: It was a retrospective study and we analyzed data of 179 patients hospitalized in the Department of Endocrinology, Diabetes and Isotope Therapy in Wroclaw Medical University (Poland) in 1976 to 2018 to create a database for statistical analysis. Results: The study group comprised of 119 women (66%) and 60 men (34%). The median age of acromegaly diagnosis was 50.5 years old for women (age range 20–78) and 46 for men (range 24–76). Metabolic disorders (hyperlipidemia, diabetes, and prediabetes) were the most frequently diagnosed complications in our study, followed by cardiovascular diseases and endocrine disorders (goiter, pituitary insufficiency, osteoporosis). BP measurement, ECG, lipid profile, fasting glucose or OGTT were performed the most often, while colonoscopy and echocardiogram were the least frequent. Conclusions: In our population we observed female predominance. We revealed a decrease in the number of patients with active acromegaly and an increase in the number of well-controlled patients. More than 50% of patients demonstrated a coexistence of cardiac, metabolic and endocrine disturbances and only 5% of patients did not suffer from any disease from those main groups. [ABSTRACT FROM AUTHOR]

Since 1994, we have been studying an extended kindred with 105 subjects (over 8 generations) residing in Itabaianinha County, in the Brazilian state of Sergipe, who have severe isolated GH deficiency (IGHD) due to a homozygous inactivating mutation (c.57 + 1G > A) in the GH releasing hormone (GHRH) receptor (GHRHR) gene. Most of these individuals have never received GH replacement therapy. They have low GH, and very low and often undetectable levels of serum IGF-I. Their principal physical findings are proportionate short stature, doll facies, high-pitched-voice, central obesity, wrinkled skin, and youthful hair with delayed pigmentation, and virtual absence of graying. The newborns from this cohort are of normal size, indicating that GH is not needed for intra-uterine growth. However, these IGHD individuals exhibit a myriad of phenotypic changes throughout the body, with a greater number of beneficial than harmful consequences. This GHRH signal disruption syndrome has been a valuable model to study the GH roles in body size and function. This reviews summarized the findings we have reported on this cohort. [ABSTRACT FROM AUTHOR]

Background: Growth hormone and insulin-like growth factor 1 are anabolic hormones that play a vital role in the growth of various physical organs. Exercise is one of the stimuli that affect GH and IGF-1 secretion. Objectives: This study aimed to compare the effect of two types of high-intensity interval training (HIIT) on plasma levels of GHand IGF-l in overweight nurses. Methods: In this study, 27 nurses were voluntarily selected and randomly assigned to three groups (9 participants for each group): 1. HIIT (type 1), including eight seconds of spring running and 12 seconds of active recovery, 2. HIIT (type 2), including a 40-meter shuttle run with maximum speed, 3. control. HIIT (type 1) was performed for four weeks, three sessions per week, each session 6 - 9 min with more than 90% HRmax. HIIT (type 2) was applied for four weeks, three sessions per week, with more than 90% HRmax. The control group did not participate in any training protocol. The serum value of GHand IGF-1 were compared in three groups. The data were analyzed by the dependent t-test and ANOVA. One-way analysis of variance (ANOVA) was used to analyze the intergroup data at P h 0.05. Results: The results showed that HIIT (type 1) and (type 2) significantly increased plasma GH (P = 0.032 in group 2 and P = 0.010 in group 1) and IGF-l (P = 0.004 in group 2 and P = 10.013 in group 1) levels in nurses. The results showed a significant difference in the variables (GH and IGF-l) among HIIT (type 1), HIIT (type 2), and control groups. Conclusions: It can be concluded that four weeks of adverse intermittent exercises are effective in increasing the concentration of GH and IGF-1 serum and decreased percentage body fat in young nurses with overweight, and proportional to the intensity of the exercise protocol response rate is different. [ABSTRACT FROM AUTHOR]

En becerras prepúberes, la kisspeptina-10 (KISS-10) estimula la liberación de hormona luteinizante (LH) y hormona foliculoestimulante (FSH), pero su acción en la hormona del crecimiento (GH) es inconsistente. La hipótesis fue que en becerras prepúberes la magnitud de liberación de LH, FSH y GH en respuesta a KISS-10 es determinada por la dosis y las concentraciones endógenas de IGF-I y leptina. Se usaron 20 becerras prepúberes (100-232 kg de peso y 7-11 meses de edad), mismas que recibieron un bolo i.v. de 5 o 50 µg de KISS-10/kg de peso. Ambas dosis de KISS-10 indujeron un incremento de LH y FSH, más no de GH. La dosis de 50 µg de KISS-10 indujo un área bajo la curva de LH y una duración del incremento de FSH mayores (P0.05). De la misma forma, las concentraciones de leptina no determinaron (P>0.05) la magnitud del incremento de LH y FSH ni las concentraciones de GH pos tratamiento. En conclusión, la GH no respondió a ninguna dosis, pero la FSH y la LH fueron sensibles al aumento de dosis de KISS-10. Además, la magnitud de respuesta de LH a KISS-10 fue determinada por las concentraciones endógenas de IGF-I, pero no de leptina.

The Endocrine Tumor Summit convened in December 2008 to address 6 statements prepared by panel members that reflect important questions in the treatment of acromegaly and carcinoid syndrome. Data pertinent to each of the statements were identified through review of pertinent literature by one of the 9-member panel, enabling a critical evaluation of the statements and the evidence supporting or refuting them. Three statements addressed the validity of serum growth hormone (GH) and insulin-like growth factor-I (IGF-I) concentrations as indicators or predictors of disease in acromegaly. Statements regarding the effects of preoperative somatostatin analog use on pituitary surgical outcomes, their effects on hormone and symptom control in carcinoid syndrome, and the efficacy of extended dosing intervals were reviewed. Panel opinions, based on the level of available scientific evidence, were polled. Finally, their views were compared with those of surveyed community-based endocrinologists and neurosurgeons.

Objectives: Cerebrovascular disease (CeVD) is a major cause of death and disability. The role of the GH/IGF-I axis on CeVD risk is controversial. Patients with GH deficiency (GHD) in the setting of hypopituitarism often exhibit CeVD predisposing factors, like low nitric oxide generation, endothelial dysfunction, increased visceral fat mass, increased levels of LDL cholesterol, and increased intima-media thickness, a surrogate marker of atherosclerosis. However, several confounders such as the primary hypothalamic–pituitary lesion, hormonal replacement therapies, consequences of surgery and radiotherapy, may influence this relationship. Therefore, we decided to assess cerebral vasoreactivity, a surrogate marker of CeVD, in adult subjects with untreated isolated GHD (IGHD) due to the same homozygous null mutation in the GHRH receptor gene. Methods: A cross-sectional study was carried out in 25 adult IGHD subjects and 25 age- and gender-matched controls. Interview, physical examination, laboratory data, intima-media thickness measurement, and transcranial Doppler were performed. The intracranial hemodynamics (mean flow velocity, pulsatility and resistance indexes) were measured, and the response to the vasodilatory stimulus by breath-holding maneuver (breath-holding index) was calculated. Results: IGHD and control groups were similar in Framingham risk score and intima-media thickness. Similarly, there was no difference in mean flow velocity, pulsatility, resistance, and breath-holding index. Conclusions: Lifetime, untreated IGHD does not cause impaired cerebral vasoreactivity. [ABSTRACT FROM AUTHOR]

This study presents the statistical results of patients who had been recently discharged from hospital within one month after their treatment in the emergency department (ED). Using routine (14,881) MCV and RDW measurements and statistical tools, we could predict acute mortality in these patients (N = 1158), adjusted for age. It is likely that an increase in the MCV and RDW parameters may correlate in some of our older patients with a poor prognosis with an increased level of circulating IGF–I, which affects red blood cell parameters. The research presents the prognostic statistics of the analyzed clinical factors as well as speculates on the potential correlation of these parameters with the regenerative potential of stem-cell compartment. Analysis shows that both MCV and RDW are statistically significant (Area Under Curve [AUC], lower CI 95% >50%) predictors of acute mortality in ED patients. The classification of patients based on their MCV threshold (= 92.2 units) indicates a proper clinical prognosis in nearly 6 of 10 subjects (AUC >58%), whereas taking into account RDW (=13.8%) indicates a proper clinical prognosis in no more than 7 of 10 individuals. The report concludes that by employing strongly fitting (95%) quadratic modeling of the ORs against the biomarkers studied, one can notice a similar relationship between MCV and RDW as diagnostic tools to predict regenerative potential and clinical outcomes in older patients. Although RDW alone had a 10% higher diagnostic value in terms of predicting early death in the emergency department in patients that were admitted to the ED and subsequently hospitalized, also taking the MCV measurement improved accuracy in predicting clinical outcomes by 2.5% compared to RDW alone. [ABSTRACT FROM AUTHOR]

Context: Acromegaly is usually a sporadic disease, but familial cases occur. Mutations in the aryl hydrocarbon receptor‐interacting protein (AIP) gene are associated with familial pituitary adenoma predisposition. However, the pathogenicity of some AIP variants remains unclear and additional unknown genes may be involved. Objective: To explore the phenotype and genotype of a large kindred carrying the p.R304Q AIP variant. Methods: The family comprised 52 family members at risk of carrying the p.R304Q AIP variant including a case with gigantism and one with acromegaly and several family members with acromegalic features. Nine family members (three trios) underwent exome sequencing to identify putative pathogenic variants. Results: We identified 31 p.R304Q carriers, and based on two cases with somatotropinomas, the disease penetrance was 6%. We observed physical signs of acromegaly in several family members, which were independent of AIP status. Serum insulin‐like growth factor‐I (IGF‐I) levels in all family members were above the mean for age and sex (IGF‐I SDS: +0.6 [CI95% +0.4‐0.9], P <.01). Exome analysis identified two candidate genes: PDE11A, known to be associated with the development of adrenal tumours, and ALG14. Ten asymptomatic p.R304Q family members (age >50 years) were screened for the PDE11A and ALG14 variant; both variants were present in five of ten persons. Conclusions: This large family adds new information on the p.R304Q AIP variant, and data suggest two new candidate genes could be associated with growth hormone excess. [ABSTRACT FROM AUTHOR]

Resequencing of Myostatin, Growth Hormone, Follistatin-A-like, Insulin-like Growth Factor I (IGF-I) and Myogenin (MYOG) genes was completed to discover novel genetic variations and assess non synonymous (ns) polymorphisms (SNPs) effect on growth related traits of channel catfish. Wild and farmed animals were used as a discovering population. Resequencing lead to the identification of 59 new variants in the five analyzed genes; 66% found in introns and 34% in coding regions. From coding regions, 14 variants were synonyms and six were ns variations. A mutation rate of one in 129 bp was estimated. Four ns variations were selected for validation and association analysis. In IGF-I two ns polymorphisms, at IGF-I19 the G wild type allele was fixed in population and for IGF-I63 the C allele had a frequency of 0.972 and for mutate allele G of 0.027. In MYOG two ns SNPs were assessed. MYOG131 presented a frequency of alleles T and A, of 0.754 and 0.246, respectively and MYOG233, with a frequency of G and C of 0.775 and 0.225, respectively. Only MYOG131 (g.529T>A) was significantly associated (P < 0.04) to some growth traits. Results suggest MYOG131 g.529T>A as candidate locus for genetic enhancement of growth traits in channel catfish. [ABSTRACT FROM AUTHOR]

The effect of a single exercise as well as exercise training on the growth hormone (GH)-insulin-like growth factor (IGF-I) axis and inflammatory cytokines was studied mainly in adults participating in individualized endurance-type sports. The gender-specific effect of exercise on these systems in adolescents is unknown. Therefore, the purpose of this study was to evaluate the effect of a typical volleyball practice on anabolic (GH, IGF-I, and testosterone) and catabolic hormones (cortisol) and inflammatory mediators (interleukin-6 [IL-6]) in elite, national team level, male (n = 14) and female (n = 13) adolescent volleyball players (13-18 years, Tanner stage 4-5). Exercise consisted of a typical 1-hour volleyball practice. Blood samples were collected before and immediately after the practice. Exercise led to significant increases in GH (0.2 +/- 0.1 to 2.7 +/- 0.7 and 1.7 +/- 0.5 to 6.4 +/- 1.4 ng x mL, in men and women, respectively, p < 0.05 for both), testosterone (6.1 +/- 0.9 to 7.3 +/- 1.0 and 2.4 +/- 0.6 to 3.3 +/- 0.7 ng x mL, in men and women, respectively, p < 0.05 for both), and IL-6 (1.1 +/- 0.6 to 3.1 +/- 1.5 and 1.2 +/- 0.5 to 2.5 +/- 1.1 pg x mL, in men and women, respectively, p < 0.002 for both). Exercise had no significant effect on IGF-I, insulin-like growth factor binding protein-3, and cortisol levels. There were no gender differences in the hormonal response to training. Changes in GH and testosterone after the volleyball practice suggest exercise-related anabolic adaptations. The increase in IL-6 may indicate its important role in muscle tissue repair. These changes may serve as an objective quantitative tool to monitor training intensity in unique occasions in team sports.

Growth hormone (GH) and insulin-like growth factor-1 (IGF-I) are pleiotropic hormones with important roles in lifespan. They promote growth, anabolic actions, and body maintenance, and in conditions of energy deprivation, favor catabolic feedback mechanisms switching from carbohydrate oxidation to lipolysis, with the aim to preserve protein storages and survival. IGF-I/insulin signaling was also the first one identified in the regulation of lifespan in relation to the nutrient-sensing. Indeed, nutrients are crucial modifiers of the GH/IGF-I axis, and these hormones also regulate the complex orchestration of utilization of nutrients in cell and tissues. The aim of this review is to summarize current knowledge on the reciprocal feedback among the GH/IGF-I axis, macro and micronutrients, and dietary regimens, including caloric restriction. Expanding the depth of information on this topic could open perspectives in nutrition management, prevention, and treatment of GH/IGF-I deficiency or excess during life.

To understand the carbohydrate utilization ability during developmental stages of Clarias magur , the mRNA levels and enzyme activity of amylase were studied. Furthermore, the transcript levels of some important growth genes like growth hormone (GH), insulin-like growth factor I (IGF-I) and insulin-like growth factor binding protein (IGFBP) were evaluated. The enzymatic activity and mRNA expression of alpha-amylase along with expression of growth-related genes were examined from hatching until 34 days post-hatching (dph) by quantitative reverse transcription-polymerase chain reaction (qRT-PCR). Subsequently, mRNA expression pattern revealed the significantly (P <.05) high transcript level of alpha-amylase during early stages and early peaks were found at 3 to 6 dph, later the expression decreased till the end of experiment. Growth-related genes like GH , IGF-I and IGFBP showed a variable level of mRNA expression pattern from 0 dph to 34 dph. However, there was no significant difference (P >.05) in the mRNA expression of growth-related genes among the different time points of the present study. Moreover, the amylase activity revealed almost same pattern as that of its mRNA expression. In general, the present results suggested that C. magur has the ability to utilize the digestible carbohydrates during the early stages and can be helpful in developing low cost feeds for larvae. • Ontogenetic development of alpha-amylase was investigated in Clarias magur larvae. • mRNA expression and activity of alpha-amylase was significantly high during initial stages. • C. magur has the ability to utilize digestible carbohydrate during early larval development. • The transcript levels of growth-related genes were insignificant among the selected time points. [ABSTRACT FROM AUTHOR]

In prepubertal heifers, kisspeptin-10 (KISS-10) stimulates the release of the luteinizing hormone (LH) and the follicle-stimulating hormone (FSH) but the growth hormone (GH) response is inconsistent. The hypothesis of this study was that in prepubertal heifers, the release of LH, FSH and GH in response to KISS-10 is determined by dose and by endogenous levels of IGF-I and leptin. Twenty heifer calves (100-232 kg of body weight and 7-11 mo of age) received an i.v. injection of 5 or 50 μg of KISS-10/kg of body weight (low and high dose, respectively). The high dose of KISS-10 induced a greater (P<0.05) response of LH (area under the curve) and FSH (duration) than the low dose. IGF-I was negatively associated (P<0.05) to LH in response to the high dose of KISS-10 but IGF-I was not associated with LH in calves treated with the low dose (P>0.05). The magnitude of FSH response as well as GH serum concentrations after KISS-10 were not altered by IGF-I levels (P>0.05). Similarly, leptin concentrations were not associated (P>0.05) with the magnitude of LH and FSH response or GH concentrations after KISS-10. In conclusion, GH did not respond to any dose of KISS-10 but FSH and LH were sensitive to an increment in the KISS-10 dose. Additionally, the magnitude of response of LH to KISS-10 was determined by endogenous levels of IGF-I but it was not associated with levels of leptin. [ABSTRACT FROM AUTHOR]

Several acquired or congenital hypothalamic abnormalities may cause growth failure (GF). We described two of these congenital abnormalities. First, a case of CHARGE syndrome, an epigenetic disorder mostly caused by heterozygous mutations in the gene encoding CHD7, a chromatin remodeling protein, causing several malformations, some life-threatening, with additional secondary hypothalamus-hypophyseal dysfunction, including GF. Second, a cohort of individuals with genetic isolated severe GH deficiency (IGHD), due to a homozygous mutation in the GH-releasing hormone (GHRH) receptor gene described in Itabaianinha County, in northeast Brazil. In this IGHD, with marked reduction of serum concentrations of IGF-I, and an up regulation of IGF-II, GF is the principal finding in otherwise normal subjects, with normal quality of life and longevity. This IGHD may unveil the effects of GHRH, pituitary GH and IGF-I, IGF-II and local GH and growth factor on the size and function of body and several systems. For instance, anterior pituitary hypoplasia, and impairment of the non-REM sleep may be due to GHRH resistance. Proportionate short stature, doll facies, high-pitched pre-pubertal voice, and reduced muscle mass reflect the lack of the synergistic effect of pituitary GH and IGF-I in bones and muscles. Central adiposity may be due to a direct effect of the lack of GH. Brain, eyes and immune system may also involve IGF-II and local GH or growth factors. A concept of physiological hierarchy controlling body size and function by each component of the GH system may be drawn from this model. [ABSTRACT FROM AUTHOR]

Introduction Obstructive sleep apnea syndrome (OSAS) prevalence in acromegaly patients is very common compared with general population. It is thought that OSAS in acromegaly patients evolve because of reversible and irreversible anatomical changes. However, reason of anatomical changes has not been known in present. Maybe, Growth Hormone (GH) and insulin-like growth factor 1 (IGF-I) levels could be an important factor in the development of anatomical changes. In this study, we aimed to determine the prevalence of OSAS in acromegaly and to show the correlation between disease activity and OSAS in acromegalic patients. Materials and Methods Newly diagnosed and treatment naive 15 acromegaly patients were included into the study. Patients were evaluated by polysomnography (PSG) recordings and hormone levels at baseline and 6 months after treatment. Results Present study showed that OSAS is more common in patients with acromegaly than general population. Moreover, there is no correlation between GH, IGF-I level and apnea-hipopnea index (AHI) both at baseline and 6 months after treatment. Discussion OSAS is a condition increased morbidity and mortality associated with acromegaly. Early diagnosis and treatment of acromegaly is important in order to prevent progression of anatomical changes leading to OSAS to an irreversible state. If OSAS and its complications had been prevented, morbidity and mortality in acromegaly patients would have been decreased.

Background: It is recommended not to measure growth hormone during oral glucose suppression (oral glucose tolerance test) during somatostatin analog treatment in acromegaly. However, we have observed that failure to suppress growth hormone in response to oral glucose tolerance test during somatostatin analog unmasks insufficient disease control and hypothesize that somatostatin analog also induces insufficient growth hormone suppression to mixed meals. Methods: We therefore compared serum growth hormone levels during two mixed meals in patients with controlled insulin-like growth factor-I levels after either surgery alone ( n = 9) or somatostatin analog treatment ( n = 9). The patients were unbiasedly matched for gender and insulin-like growth factor-I and studied twice in the following order: (1) during a 6 h growth hormone day curve including two mixed meals and (2) during a 3 h growth hormone profile including 60 min fasting followed by a 2-h oral glucose tolerance test. Results: During the day curve growth hormone levels were elevated in the somatostatin analog group ( P = 0.008) and growth hormone levels 1 h after each meal declined significantly only in the surgery group ( P = 0.02). During the oral glucose tolerance test the two groups had similar growth hormone levels prior to the glucose load ( P = 0.6), whereas a significant 66% suppression was observed after glucose only in the surgery group ( P = 0.001). Conclusions: (1) Patients controlled by somatostatin analog fail to suppress growth hormone in response to both mixed meals and oral glucose tolerance test (2) This phenomenon is likely to result in elevated serum growth hormone levels during everyday life in somatostatin analog-treated patients, (3) We postulate that measuring growth hormone levels during oral glucose tolerance test is useful to unmask potential somatostatin analog under-treatment in the presence of 'safe' insulin-like growth factor-I levels. [ABSTRACT FROM AUTHOR]

The study was conducted to determine the effects of chitosan on the concentrations of GH and IGF-I in serum and small intestinal morphological structure of piglets, in order to evaluate the regulating action of chitosan on weaned pig growth through endocrine and intestinal morphological approaches. A total of 180 weaned pigs (35 d of age; 11.56±1.61 kg of body weight) were selected and assigned randomly to 5 dietary treatments, including 1 basal diet (control) and 4 diets with chitosan supplementation (100, 500, 1,000 and 2,000 mg/kg, respectively). Each treatment contained six replicate pens with six pigs per pen. The experiment lasted for 28 d. The results showed that the average body weight gain (BWG) of pigs was improved quadratically by dietary chitosan during the former 14 d and the later 14 d after weaned (p

The objective of this study was to determine the effects of GDF-9, IGF-I, and GH alone or combined on preantral follicle survival, activation and development after 1 and 7 days of in vitro culture. Either fresh (non-cultured) or cultured ovarian tissue was processed for histological and fluorescence analysis. For all media tested, the percent of normal follicles was greater when compared to minimum essential medium supplemented (MEM+) alone, except when ovarian tissue was cultured with GDF-9/IGF-I or GDF-9/GH (P < 0.05). Fluorescence analysis showed that the percent of viable follicles after 7 days of culture was similar for non-cultured tissue and for all treatments tested. The percent of primordial follicles was reduced (P < 0.05) and there was a significant and concomitant increase in the percent of intermediate and primary follicles in all treatments tested after 7 days of culture when compared to non-cultured tissue. After 7 days of culture, the highest percent of intermediate follicles was observed with IGF-I/GH (61.3%), and the highest percent of primary follicles was achieved with IGF-I (57.7%). After 7 days of culture in MEM+ containing GDF-9, IGF-I and GH alone or in all associations, a significant increase in follicular diameter was observed when compared to MEM+ alone and non-cultured tissue. In conclusion, GDF-9, IGF-I and GH alone or in combination maintain preantral follicle survival and promote primordial follicle activation. Nevertheless, the data showed that IGF-I/GH and IGF-I alone are efficient in promoting the transition from primordial to intermediate follicles and from intermediate to primary follicles, respectively.

Three experiments (EXP) were conducted to determine the role of insulin-like growth factor-I (IGF-I) in the control of growth hormone (GH) and LH secretion. In EXP I, prepuberal gilts, 65 ± 6 kg body weight and 140 days of age received intracerebroventricular (ICV) injections of saline (n = 4), 25 μg (n = 4) or 75 μg (n = 4) IGF-I and jugular blood samples were collected. In EXP II, anterior pituitary cells in culture collected from 150-day-old prepuberal gilts (n = 6) were challenged with 0.1, 10 or 1000 nM [Ala15]-h growth hormone-releasing hormone-(1-29)NH2 (GHRH), or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 1000 nM GHRH. Secreted GH was measured at 4 and 24 h after treatment. In EXP III, anterior pituitary cells in culture collected from 150-day-old barrows (n = 5) were challenged with 10, 100 or 1000 nM gonadotropin-releasing hormone (GnRH) or 0.01, 0.1, 1, 10, 30 nM IGF-I individually or in combinations with 100 nM GnRH. Secreted LH was measured at 4 h after treatment. In EXP I, serum GH and LH concentrations were unaffected by ICV IGF-I treatment. In EXP II, relative to control all doses of GHRH increased (P < 0.01) GH secretion. Only 1, 10, 30 nM IGF-I enhanced (P < 0.02) basal GH secretion at 4 h, whereas by 24 h all doses except for 30 nM IGF-I suppressed (P < 0.02) basal GH secretion compared to control wells. All doses of IGF-I in combination with 1000 nM GHRH increased (P < 0.04) the GH response to GHRH compared to GHRH alone at 4 h, whereas by 24 h all doses of IGF-I suppressed (P < 0.04) the GH response to GHRH. In EXP III, all doses of IGF-I increased (P < 0.01) basal LH levels while the LH response to GnRH was unaffected by IGF-I (P > 0.1). In conclusion, under these experimental conditions the results suggest that the pituitary is the putative site for IGF-I modulation of GH and LH secretion. Further examination of the role of IGF-I on GH and LH secretion is needed to understand the inhibitory and stimulatory action of IGF-I on GH and LH secretion.

Objective Experimental models demonstrate an important role of GH in retinal development. However, the interactions between GH and the neuro-vascularization of the human retina are still not clear. A model of untreated congenital isolated GH deficiency (IGHD) may clarify the actions of GH on the retina. The purpose of this work was to assess the retinal neuro-vascularization in untreated congenital IGHD (cIGHD). Design In a cross sectional study, we performed an endocrine and ophthalmological assessment of 25 adult cIGHD subjects, homozygous for a null mutation (c.57 + 1G > A) in the GHRH receptor gene and 28 matched controls. Intraocular pressure measurement, retinography (to assess the number of retinal vascular branching points and the optic disc and cup size), and optical coherence tomography (to assess the thickness of macula) were performed. Results cIGHD subjects presented a more significant reduction of vascular branching points in comparison to controls (91% vs. 53% [ p = 0.049]). The percentage of moderate reduction was higher in cIGHD than in controls ( p = 0.01). The percentage of individuals with increased optic disc was higher in cIGHD subjects in comparison to controls (92.9% vs. 57.1%). The same occurred for cup size (92.9% vs. 66.7%), p < 0.0001 in both cases. There was no difference in macula thickness. Conclusions Most cIGHD individuals present moderate reduction of vascular branching points, increase of optic disc and cup size, but have similar thickness of the macula. [ABSTRACT FROM AUTHOR]

As a result of our publication of the first patients with short stature due to a mutation in the gene for PAPP-A2 the question, “Why did you continue to study these patients when they were not more than 2 SDS below normal?” has been proposed surprisingly frequently. We would like to communicate our opinions on why these patients were studied and share the experience on how this process took place. In addition, the choice of treatment is also discussed. We believe that this discovery process is a good example of good clinical practice and international collaboration. [ABSTRACT FROM AUTHOR]