Increase In Growth Hormone Levels Research Articles

Engaging in Short-Term Moderate-Intensity Exercise Increases Growth Hormone Levels in Individuals with Obesity

Objectives. This study aimed to analyze the effect of a four-week moderate-intensity exercise regimen on increasing growth hormone (GH) levels in individuals with obesity. Materials and methods. A total of 25 female individuals aged 20-25 years, with a body mass index (BMI) of 27.50-37.00 kg/m², were involved in the study and randomly divided into two groups, namely the control group (CON; n = 12) and the moderate-intensity exercise group (MIE; n = 13). The moderate-intensity exercise regimen (treadmill exercise for 30 minutes at 60-70% of HRmax, and resistance exercise for 30 minutes at 60-70% of 1RM) was conducted 3 times per week for a period of 4 weeks. Blood samples from participants were collected pre- and post-exercise sessions, and GH levels were analyzed using the Enzyme-Linked Immunosorbent Assay method. Data analysis techniques used the paired sample t-test with a significance level of 5 %. Results. The paired sample t-test results of GH levels between the pre-exercise and post-exercise sessions in the CON group showed a change from (1291.79 ± 383.76 to 1151.53 ± 484.80 pg/mL; p = 0.694), while the MIE group demonstrated the following dynamics of change — from (1161.79 ± 133.72 to 2103.83 ± 357.09 pg/mL; p = 0.006). Conclusions. The main findings of this study revealed that after implementing a four-week moderate-intensity exercise intervention, a significant increase in GH levels was observed in obese females.

Central growth hormone action regulates neuroglial and proinflammatory markers in the hypothalamus of male mice

Growth hormone (GH) action in specific neuronal populations regulates neuroendocrine responses, metabolism, and behavior. However, the potential role of central GH action on glial function is less understood. The present study aims to determine how the hypothalamic expression of several neuroglial markers is affected by central GH action in male mice. The dwarf GH- and insulin-like growth factor-1 (IGF-1)-deficient Ghrhrlit/lit mice showed decreased mRNA expression of Nes (Nestin), Gfap, Iba1, Adgre1 (F4/80), and Tnf (TNFα) in the hypothalamus, compared to wild-type animals. In contrast, transgenic overexpression of GH led to high serum GH and IGF-1 levels, and increased hypothalamic expression of Nes, Gfap, Adgre1, Iba1, and Rax. Hepatocyte-specific GH receptor (GHR) knockout mice, which are characterized by high serum GH levels, but reduced IGF-1 secretion, showed increased mRNA expression of Gfap, Iba1, Tnf, and Sox10, demonstrating that the increase in GH levels alters the hypothalamic expression of glial markers associated with neuroinflammation, independently of IGF-1. Conversely, brain-specific GHR knockout mice showed reduced expression of Gfap, Adgre1, and Vim (vimentin), indicating that brain GHR signaling is necessary to mediate GH-induced changes in the expression of several neuroglial markers. In conclusion, the hypothalamic mRNA levels of several neuroglial markers associated with inflammation are directly modulated by GHR signaling in male mice.

The multiple roles of GH in neural ageing and injury.

Advanced age is typically associated with a decrease in cognitive function including impairment in the formation and retention of new memories. The hippocampus is critical for learning and memory, especially spatial learning, and is particularly affected by ageing. With advanced age, multiple neural components can be detrimentally affected including a reduction in the number of neural stem and precursor cells, a decrease in the formation of adult born neurons (neurogenesis), and deficits in neural circuitry, all of which ultimately contribute to impaired cognitive function. Importantly, physical exercise has been shown to ameliorate many of these impairments and is able to improve learning and memory. Relevantly, growth hormone (GH) is an important protein hormone that decreases with ageing and increases following physical exercise. Originally described due to its role in longitudinal growth, GH has now been identified to play several additional key roles, especially in relation to the brain. Indeed, the regular decrease in GH levels following puberty is one of the most well documented components of neuroendocrine ageing. Growth hormone deficiency (GHD) has been described to have adverse effects on brain function, which can be ameliorated via GH replacement therapy. Physical exercise has been shown to increase circulating GH levels. Furthermore, we recently demonstrated the increase in exercise-mediated GH is critical for improved cognitive function in the aged mouse. Here we examine the multiple roles that GH plays, particularly in the aged brain and following trauma, irradiation and stroke, and how increasing GH levels can ameliorate deficits in cognition.

GLP-1 Receptor Agonists Induce Growth Hormone Secretion in Healthy Volunteers.

Growth hormone (GH) is an essential regulator of growth, body composition and fuel metabolism and, consequently, GH secretion is under the feedback control of numerous nutritional and endocrine mediators. Glucagon-like peptide 1 receptor agonists (GLP-1RAs) have been shown to exert pleiotropic effects, including stimulation of the activity of the hypothalamic-pituitary-adrenal axis. As GLP-1RAs exert multiple metabolic effects, we hypothesised that they may also affect the secretion of GH and examined the effect of a short-acting and a long-acting GLP-1 RA on GH secretion. This is a post hoc analysis of data from clinical trials. Two separate single-group open-label clinical trials were carried out in the ambulatory care setting with a duration of 1 and 21days, respectively. Healthy adult male and female volunteers with no chronic illnesses or use of daily medicines were recruited for the study. The two interventions were: study 1, single dose of 10µg exenatide administered subcutaneously (s.c.); study 2, 0.6mg liraglutide administered s.c. once daily for 21days. Administration of a single dose of exenatide (study 1) caused a clear increase in GH levels, peaking between 60 and 120min post-administration. There was also a small but statistically significant decrease in luteinising hormone and testosterone levels 120min after exenatide dosing. Administration of the long-acting GLP-1RA liraglutide daily for 21 days (study 2) elicited an increase in GH levels with no change in insulin-like growth factor-1 (IGF-1) concentrations after 3weeks of treatment. The results show that the administration of GLP-1RAs may elicit an increase in growth hormone levels. GLP-1 signalling may be a novel mechanism of regulation of GH secretion. This finding needs to be replicated in the placebo-controlled trial. NCT02089256 and NCT03160261.

OR27-4 Placebo-Controlled and Open-Label Extension Study of a Novel Hepatic-Targeted Antisense Cimdelirsen (IONIS-GHR-LRx) Under Investigation in Acromegaly Patients

Abstract Cimdelirsen (IONIS-GHR-LRx; ISIS 766720) is a novel, ligand-conjugated, hepatic-targeted investigative antisense molecule designed to reduce growth hormone receptor (GHr) synthesis, thereby inhibiting deleterious effects of growth hormone (GH) hypersecretion and reducing circulating insulin-like growth factor-1 (IGF-1) levels in acromegaly patients. Methods Cimdelirsen was evaluated in a 4-month double-blind, placebo-controlled phase 2 study (DBL) in uncontrolled acromegaly patients (IGF-1>1.3-<5xULN) treated with stable long-acting somatostatin receptor ligand (SRL) injections (NCT03548415). Due to COVID-19 pandemic, the study closed early resulting in smaller cohorts than planned. While no longer powered to assess Day 141 primary endpoint (PE), the study permitted placebo-controlled evaluation of safety and efficacy. The final analysis included 41 patients in the cimdelirsen low dose (60 and 80 mg; n=22), high dose (120 and 160 mg; n=7) or placebo (n=12) cohorts. 39 of these patients subsequently entered an open label extension (OLE) safety study where all patients were treated with cimdelirsen and at the time of interim analysis, 23 patients were treated for ≥ 1 year (NCT03967249).Patient reported outcomes were assessed using the validated ACROQoL and an acromegaly symptoms questionnaire. Results Cimdelirsen treatment resulted in a significant, dose dependent reduction in GH-binding protein (GHBP), a biomarker of hepatic GHR reduction: -2% placebo, -43% low dose, -64% high dose; p<0.001. Importantly, GHBP reductions were not associated with fasting GH increases. The GH mean change from baseline to PE was 1 ng/mL placebo, 0 ng/mL low dose and 1 ng/mL high dose (p>0.5). GHBP reductions without GH increases were maintained for up to 1 year of treatment in all patients.Integrated AUC for IGF-1 calculated after GHBP had reached near-maximal reductions (Day 57 to PE) demonstrated dose-dependent reductions that were significant at the high dose (+692%*day placebo, -460 low dose, and -1378 high dose; p=0.21 and 0.05 for the low dose and high dose groups, respectively). A greater reduction in IGF-1 AUC was observed in patients who had higher IGF-1 levels at baseline.Patients with higher IGF-1 levels showed significant improvements in ACROQoL at the PE; all patients demonstrated improvements after 1 year. Importantly, high-dose cimdelirsen improved sweating and headaches at PE.In both studies, there were no drug-related SAEs. The most frequently reported TEAE were UTI (16.1%) and COVID-19 (12.8%) in DBL and OLE, respectively. No safety signals were observed including no ALT elevation >3×ULN and no thrombocytopenia (<100 10^3/uL). Glycemic control remained stable and showed no worsening of HbA1c. Conclusion Once monthly SC cimdelirsen injections demonstrated long-term safety, were well-tolerated, and resulted in significant reductions in GHBP and IGF-1 AUC without increased GH levels. Cimdelirsen also improved PRO, collectively supporting further development of this novel, liver-directed potential therapy for uncontrolled acromegaly. Presentation: Tuesday, June 14, 2022 10:30 a.m. - 10:45 a.m.

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.

Does the Rhythmic Gymnastics Training Affect Serum Bone Resorption and Oxidative Stress Markers?

Introduction: Rhythmic gymnastics training (RGT) includes intensive anaerobic loads, therefore it may cause oxidative stress (OS) and then consequently might negatively affect bone metabolism and nitric oxide (NO) levels which is related to vasodilation and bone metabolism. This study investigated the effects of chronic RGT on the markers of serum bone metabolism, OS, and NO levels together, which is yet unclear. Materials and methods: 16 girls rhythmic gymnasts (athletic group, AG; 10.33 ± 1.79, years) and 13 controls (CG; 9.23 ± 1.00 years) participated in this study. Type 1 collagen carboxy-terminal cross-linked telopeptide (ICTP) as bone resorption marker (using ELISA method), alkaline phosphatase (ALP), parathyroid hormone (PTH), calcium (Ca), and growth hormone (GH) as bone metabolism markers; Total oxidant /antioxidant status ratio (TOS/TAS) as OS index (OSI) and NO levels; Troponin-I (Tn-I), and CK-MB levels, alanine aminotransferase (ALT), aspartate amino transferase (AST), creatine kinase (CK) as muscle injury markers; Some hematological parameters including hemogram were measured by standard methods. Results: Serum ICTP1 (p= 0.01) and GH (47.4 %) levels of AG were significantly higher than CG, whereas Ca level (p= 0.04) and body fat rate values was lower (p= 0.00). There is no significant difference between the groups for other parameters. Conclusions: The results suggest that RGT training did not significantly affect OS and NO levels that can cause anemia. But besides the increased GH levels, bone development can be affected negatively in child gymnasts due to the increased ICTP and decreased Ca levels. Thus, a calcium-rich diet and regular observation of bone metabolism markers are recommended. Keywords: Rhythmic gymnastics, Oxidative stress, Bone destruction, Nitric oxide.

The evaluation of breast findings detected through different visualisation techniques in acromegaly patients — a retrospective study

It is known that the increased growth hormone (GH) and insulin-like growth factor-1 (IGF-1) have mitogenic and antiapoptotic properties in breast cells in acromegaly. Our study aims to evaluate breast findings in patients with acromegaly by comparing them to the control group. Sixty-one patients followed with acromegaly diagnosis and 180 healthy controls were included in our study. Demographic data, laboratory results, Breast Imaging-Reporting and Data System (BI-RADS) scores, and breast density evaluated via mammography, malign and benign breast lesions evaluated via mammography, breast ultrasonography (USG), and breast magnetic resonance imaging (MRI) of patients were compared to the control group. While BI-RADS scores were similar in patient and control groups, breast density in acromegaly patients was found out to be higher compared to the control group (p = 0.754, p = 0.001, respectively). In acromegaly patients, the breast calcification rate was higher than controls (p = 0.021). t was observed that mass frequency in USG in acromegaly patients increased when GH level increased as well (p = 0.021). No difference was detected between benign and malign breast lesions diagnosed histopathologically ( p = 0.031, p = 0.573, respectively). There was not any difference in terms of BI-RADS scores, breast types, and breast lesions in acromegaly patients that were in remission and not in remission (p > 0.05). Benign and malign breast lesions were found out to be similar to the control group, although breast density rate was detected to be higher in acromegaly patients. A regular follow-up is required in these patients via suitable breast visualization techniques considering their age and clinical status due to mass formation risk derived from increased GH level and extreme breast density despite the absence of any detected breast lesion frequency in acromegaly patients.

Effects of 4-Hexylresorcinol on Craniofacial Growth in Rats.

4-Hexylresorcinol (4HR) has been used as a food additive, however, it has been recently demonstrated as a Class I histone deacetylase inhibitor (HDACi). Unlike other HDACi, 4HR can be taken through foods. Unfortunately, some HDACi have an influence on craniofacial growth, therefore, the purpose of this study was to evaluate the effects of 4HR on craniofacial growth. Saos-2 cells (osteoblast-like cells) were used for the evaluation of HDACi and its associated activities after 4HR administration. For the evaluation of craniofacial growth, 12.8 mg/kg of 4HR was administered weekly to 4 week old rats (male: 10, female: 10) for 12 weeks. Ten rats were used for untreated control (males: 5, females: 5). Body weight was recorded every week. Serum and head samples were collected at 12 weeks after initial administration. Craniofacial growth was evaluated by micro-computerized tomography. Serum was used for ELISA (testosterone and estrogen) and immunoprecipitation high-performance liquid chromatography (IP-HPLC). The administration of 4HR (1–100 μM) showed significant HDACi activity (p < 0.05). Body weight was significantly different in male rats (p < 0.05), and mandibular size was significantly smaller in 4HR-treated male rats with reduced testosterone levels. However, the mandibular size was significantly higher in 4HR treated female rats with increased growth hormone levels. In conclusion, 4HR had HDACi activity in Saos-2 cells. The administration of 4HR on growing rats showed different responses in body weight and mandibular size between sexes.

Impact of Experience on Outcomes After Endoscopic Transsphenoidal Surgery for Acromegaly

Acromegaly is a syndrome of metabolic alterations secondary to increased growth hormone levels from a somatotroph pituitary adenoma. A multidisciplinary approach beginning with surgery, followed by adjuvant radiation or medical therapy for residual disease, is considered standard of care. Several factors affect the likelihood of remission after surgery, but the impact of surgical experience on remission rates has not been adequately assessed. Retrospective review of 203 patients, divided into 2 eras (era 1, 102 patients; era 2, 101 patients) of patients who underwent transsphenoidal surgery for acromegaly by a single surgeon over 11 years, was performed, determining the effect of surgical experience on rates of remission and various complications. Remission was defined according to the 2014 Endocrine Society Clinical Practice Guideline. The rate of surgical remission was 40.6% (62.9% among noninvasive adenomas). Rates of surgical remission significantly improved in the latter half of this cohort (31.2% in the first half vs. 50% in the second half), despite other factors being comparable. On multivariate analysis, surgeon experience, cavernous sinus invasion, and preoperative growth hormone levels affected the rates of surgical remission. Rates of cerebrospinal fluid leak and hypopituitarism were lower in the second half, whereas resolution of acromegaly-associated comorbidities was increased. We report, in this large single-surgeon review of endoscopically operated acromegaly cases, increased rates of surgical remission and reduced complications with increasing surgeon experience. The overall experience of the treating team in dealing with perioperative and intraoperative factors also contributes to improved outcomes.

High-intensity interval exercise test stimulates growth hormone secretion in children

Backgroundexercise stimulates growth hormone (GH) secretion and may serve as a promising physiological test for the diagnosis of GH deficiency. However, exercise standardization for a feasible GH test is still lacking. The aim of the present study was to examine the GH secretion to high intensity interval exercise. MethodsSeventeen children (12.4 ± 2.6 years) with impaired growth rate performed high-intensity interval exercise test (HIIE) that included 10 intervals of 15 s all out pedaling against resistance determined by age, sex and weight on a cycle ergometer with 1-min active rest between each interval. Power output measurements were collected during the test. Blood samples were collected before, immediately after, 30, 45, and 60min after the beginning of the exercise test. GH response was compered to pharmacological provocation test (clonidine or glucagon). ResultsHIIE led to a significant increase in GH levels (p < 0.001), with high correlation to GH response following pharmacological stimulation (r = 0.82, r = 0.80 for clonidine and glucagon respectively, p < 0.001) A significant correlation was found between mean peak power to body weight and the GH response (r = 0.50, p = 0.04). 83% of the participants who reached peak power > 10 watts/kg had normal GH secretion. ConclusionsHIIE is a brief and individualized exercise protocol that may be used as a physiological provocation test for GH secretion. There might be a minimum of anaerobic power needed to induce adequate GH response during HIIE.

Acute growth hormone response to concurrent strength–sprint training with different orders in strength-trained men

The purpose of this study was to investigate the effect of the intra-session order of concurrent strength-sprint training on the acute growth hormone response. Nine strength-trained students (age 24.1 ± 4.1) performed two different concurrent exercise orders: strength–sprint (STS) and sprint–strength (SPS). Strength training consisted of three sets of ten repetitions with 10RM for four exercises: bench press, lat pulldown, squat and shoulder press. Sprint exercise consisted of eight repetitions of 30-m maximal sprint running with 45-s rest periods between repetitions. In both exercise orders, the subjects rested for 10 min after the completion of the first part of the concurrent training session. Blood samples were collected before, between exercise modalities, and immediately after the concurrent training sessions. A significant increase in growth hormone levels occurred in response to single sessions of concurrent strength–sprint training, but no significant difference was observed between the two different orders of concurrent training (STS vs. SPS) regarding the acute growth hormone response. In general, performing sprint training before or after strength training not only imposes no inhibitory effect on the growth hormone response to strength training, but also increases the hormone’s overall response.

Stimulation of endogenous pulsatile growth hormone secretion by activation of growth hormone secretagogue receptor reduces the fat accumulation and improves the insulin sensitivity in obese mice.

Obese individuals often show low growth hormone (GH) secretion, which leads to reduced lipid mobilization and further fat accumulation. Pharmacological approaches to increase GH levels in obese individuals by GH injection or GH-releasing hormone receptor agonist showed promising effects on fat reduction. However, side effects on glucose metabolism and the heavy costs on making large peptides hindered their clinical application. Here, we tested whether stimulation of endogenous GH secretion by a synthetic GH secretagogue receptor (GHSR) agonist, hexarelin, improved the metabolism in a hyperphagic obese mouse model. Male melanocortin 4 receptor knockout mice (MC4RKO) were pair-fed and received continuous hexarelin (10.56μg/day) or vehicle infusion by an osmotic pump for 3-4weeks. Hexarelin treatment significantly increased the pulsatile GH secretion without detectable alteration on basal GH secretion in MC4RKO mice. The treated mice showed increased lipolysis and lipid oxidation in the adipose tissue, and reduced de novo lipogenesis in the liver, leading to reduced visceral fat mass, reduced triglyceride content in liver, and unchanged circulating free fatty acid levels. Importantly, hexarelin treatment improved the whole-body insulin sensitivity but did not alter glucose tolerance, insulin levels, or insulin-like growth factor 1 (IGF-1) levels. The metabolic effects of hexarelin were likely through the direct action of GH, as indicated by the increased expression level of genes involved in GH signaling pathways in visceral adipose tissues and liver. In conclusion, hexarelin treatment stimulated the pulsatile GH secretion and reduced the fat accumulation in visceral depots and liver in obese MC4RKO mice with improved insulin sensitivity without altered levels of insulin or IGF-1. It provides evidence for managing obesity by enhancing pulsatile GH secretion through activation of GHSR in the pituitary gland.

Similar Pattern of Increase in FIX Levels in Female Carriers and Males with Hemophilia B Leyden

Hemophilia B is a congenital X-linked recessive bleeding disorder that occurs as a result of mutations at the long (q) arm of the X chromosome at position 27. Hemophilia B affects 1 in 30,000 males; however the incidence in Ireland is more than double the international incidence and affects 1 in 12,500 male births. Hemophilia B Leyden is a sub-type of hemophilia B first recognized in 1970 in Leyden in the Netherlands. There are more than 20 genetic mutations that result in hemophilia B Leyden. These mutations cluster at three regions within the proximal promoter region of the F9 gene including mutations in nucleotides c.-34 and c.-35 (-5 and -6 legacy numbering) in almost half the cases, mutations around nucleotide c.-49 (-20) and mutations around nucleotide c.-19 (+10). Point mutations associated with hemophilia B Leyden interfere with F9 gene transcription via binding of F9 promoter to ONECUT1 in patients with c.-35 mutation, HNF4a (hepatocyte nuclear factor 4 alpha) in patients with c.-19 mutation and C/EBPa (enhancer-binding protein alpha) in patients with c.-49 mutation. A characteristic feature of hemophilia B Leyden is progressive rise in FIX:C level from the time of puberty to reach lower normal level in young adults. This led to the widely accepted believe that the increase in FIX:C level in hemophilia B Leyden is due to the effect of the androgens surge at puberty. Androgens and anabolic steroids were used for prophylactic treatment in patients with hemophilia B Leyden in a limited number of patients. Recent evidence from animal studies using hypophysectomized hemophilia B Leyden mouse model convincingly demonstrated the pre-eminent role of growth hormone (GH) in regulating the age-dependent increase in FIX:C levels. FIX:C levels were only restored to 10% of pre-hypophysectomy levels by exogenous administration of dihydrotestosterone or oestrodiol but were restored to 80% of pre-hypophysectomy levels by exogenous administration of GH. We investigated the pattern of the increase in FIX:C in 14 male children and four female children from seven different Irish families attending the National Haemophilia Centre at Children's Health Ireland, Crumlin. The hemizygous presence of hemophilia B Leyden associated variant c.35G&amp;gt;A was confirmed by standard dideoxysequence analysis in all children. To evaluate the timing of increase in plasma FIX:C levels, we measured FIX:C levels using automated one stage assay. Serial measurement of FIX:C in male children with hemophilia B leyden demonstrated an increase of FIX:C from severe/moderate levels at the first year of life to mild FIX:C levels within the first 3 years of life. In all 14 male children with hemophilia B Leyden, FIX:C levels increased gradually throughout childhood with more pronounced increase in FIX:C at the time of puberty (Figure 1-A). The increase in FIX:C levels coincided with the known physiological increase in GH levels. Growth hormone level is low during infancy and increases but remains stable at low levels during early childhood, until just before puberty when GH secretion surges to the highest lifetime peak. All four female carriers of hemophilia B Leyden showed low levels of FIX:C at diagnosis associated with variable bleeding symptoms (Figure 1-B). One female child had very low FIX:C level at diagnosis in the moderate hemophilia range (0.04 iu/ml), while all other three female children had low FIX:C levels at the mild hemophilia range at diagnosis (0.13 iu/ml, 0.27 iu/ml and 0.46 iu/ml respectively). Low FIX:C level in those female carriers is likely due to skewed inactivation of the unaffected X chromosome during embryogenesis (lyonization) as no child had compound heterozygosity for the F9 gene mutation and none of the children showed clinical features of Turner syndrome or testicular feminization syndrome. Serial measurement of FIX:C levels in those symptomatic female carriers of hemophilia B Leyden showed similar gradual increase in FIX:C levels during childhood with more steep increase at puberty. Our findings further assert that gender and sex hormones has no influence in the increase of FIX:C level in hemophilia B patients. Figure 1 Disclosures Nolan: Sobi: Other: personal fees; Bayer, CSL Behring, and Sanofi.: Other: sponsorship; Sanofi: Other: PI for sponsor-(Sanofi-) led clinical trial.

Reduced Growth Hormone Response to Anaerobic Exercise Among Children With Overweight and Obesity.

Hejla, D, Dror, N, Pantanowitz, M, Nemet, D, and Eliakim, A. Reduced growth hormone response to anaerobic exercise among children with overweight and obesity. J Strength Cond Res 36(8): 2194-2197, 2022-The aim of the present study was to examine the effect of an anaerobic exercise test on growth hormone (GH) secretion in children with overweight and obesity compared with children with normal weight. Fifteen children with overweight (body mass index percentile [BMI%ile] ≥85 < 95) and obesity (BMI%ile ≥95) and 10 children with normal weight (BMI%ile >5 < 85) participated in the study. Subjects performed a modification of the Wingate anaerobic test (WAnT), with 10 bouts of 15-second cycling separated by 1 minute of rest. Blood samples for GH and lactate were collected before and 15, 30, 45, and 60 minutes after the beginning of the exercise test. There was a significant increase in GH levels following the modified repeated WAnT in both groups, but the increase in GH levels was significantly greater among the normal weight children compared with those with overweight and obesity ( p < 0.003). Seven of the 10 subjects with normal weight had GH increase above the threshold for GH sufficiency compared with only 2 subjects with overweight and obesity. Growth hormone response to the modified repeated WAnT was significantly reduced among children with overweight and obesity compared with those with normal weight. Anaerobic interval-type training may not be a sufficient exercise alternative to stimulate appropriate GH levels among children with obesity.

The acute and chronic effects of resistance training with blood flow restriction on hormonal responses in untrained young men: A comparison of frequency

The present study aimed to determine the effect of low-intensity training with blood flow restriction (BFR) on the response rate of anabolic hormones. Forty healthy and untrained young men, aged 18 to 25 years old, were randomly divided into five groups: one session of BFR training (BFR1), two sessions of BFR training (BFR2), one session of resistance training without BFR (WBFR1), two sessions of resistance training without BFR (WBFR2), and the control group (without training). BFR groups had three sets of 20 repetitions with 20-30% 1RM, and none-BFR groups had three sets of 10 repetitions with 70-80% 1RM for six weeks. Both BFR1 and WBFR1 groups trained 3day a week (1 session in a day and three sessions a week), BFR2 and WBFR2 groups trained three days a week (but two sessions a day and six sessions in a week) and Control group did not perform any training. The mean changes in growth hormone(GH), testosterone(TS), and vascular endothelial growth factor (VEGF) hormones were determined by ELISA technique before, after a first training session and after six weeks of the training program. To the analysis of data, two way repeated measures ANOVA at a significant level of P&lt;0.05 also were used. The results showed a significant increase in GH levels in each of the four training groups as compared with the pre-test and the control group after a first training session and after six weeks of the training program (P&lt;0.05). There was no significant increase in TS levels in each of the four training groups, as compared with the pre-test and the control group in both acute and chronic TS response (P&gt;0.05). Only the WBFR1 group did not significantly increase in VEGF levels after the first training session (P&gt;0.05). In chronic VEGF response, there were no significant changes observed in all training groups as compared with the control group(P&gt;0.05). Despite the effectiveness of low-intensity BFR training, such as high-intensity resistance training on hormonal responses, two sessions per day training with the same volume does not necessarily result in larger responses in all hormones than one session per day training.

IGF-1 is an independent predictor of retinal arterioles remodeling in subjects with uncontrolled acromegaly.

Cardiovascular disease is one of the main causes of morbidity in active acromegaly due to the increased prevalence of risk factors and arterial consequences of increased growth hormone levels. No in vivo study has evaluated the consequences of acromegaly on the retinal microvasculature. The aim of this study was to identify in vivo the presence of morphological alterations of retinal arterioles in subjects with acromegaly. Single-center retrospective study of a cohort of 60 subjects with acromegaly, matched to 60 controls, who were referred for adaptive optics camera (AOC) from September 2014 to December 2016. Of the subjects with acromegaly, 19 had an active disease (AD) and 41 a controlled disease (CD) based on the IGF1 ratio (IGF1r). Retinal arteriolar remodeling was previously assessed using adaptive optics camera (AOC) in order to measure wall-to-lumen ratio (WLR), wall thickness (WT), internal diameter (ID) and wall cross sectional area (WCSA). WLR was significantly higher in AD subjects compared to CD subjects and controls (AD: 0.311 ± 0.06, CD: 0.279 ± 0.04, controls: 0.281 ± 0.04, P = 0.031). A significant positive correlation was observed between WLR and IGF-1r (R2 = 0.215, P < 0.001), even after adjustment for gender, age, systolic blood pressure (SBP) and the presence of dopamine agonist treatment (R2 = 0.406, P < 0.001). Retinal arteriolar anatomical indices were comparable between CD and controls. Active acromegaly is associated with the presence of small retinal arteriolar remodeling. These results provide new perspectives to better stratify cardiovascular risk and consequently optimize treatment in acromegaly.

Morphometric Alterations of the Sphenoid Ostium and other Landmarks in Acromegaly: Anatomical Considerations and Implications in Endoscopic Pituitary Surgery.

The sphenoid ostium (SO) is an important landmark for the endoscopic surgeon. Changes in size and position of the SO and variations in other skull base landmarks in acromegalics have not been adequately evaluated. The authors evaluated the morphometry and location of the SO and other landmarks in acromegaly and compared these findings with those in nonfunctioning pituitary adenomas (NFPAs). In this retrospective case-control study, the dimensions and location of the SO and other skull base landmarks were radiologically evaluated in 18 patients with growth hormone (GH)-secreting adenomas. These findings were analyzed in relation to preoperative GH levels and compared with 18 age- and sex-matched controls with NFPAs. The dimensions of the SO were significantly larger in the GH-adenoma group (P < 0.05). The SO was further from the midline (P = 0.04) and closer to the sphenopalatine foramen (SPF) (P = 0.02) in the GH-adenoma group, and this finding correlated with increasing preoperative GH levels. Acromegalics demonstrated larger intracavernous carotid diameters (P = 0.05) and smaller intercarotid distances than the patients with NFPAs (P = 0.02). The SO is larger and located higher up in the sphenoid face and closer to the SPF in patients with GH adenomas. Increasing GH levels in these patients correlate with the upward and lateral displacement of the SO. These patients demonstrate larger intracavernous carotid diameters and smaller intercarotid distances than patients with NFPAs. These morphological alterations are of particular relevance to the pituitary surgeon.

78 Effects of Isomaltooligosaccharide and Bacillus supplementation on sow performance, serum metabolite and oxidative status in serum and placenta

Abstract This study investigated the effects of Isomaltooligosaccharide (IMO) and Bacillus supplementation on sow performance, serum metabolite and oxidative status in serum and placenta. One hundred and thirty multiparous gestating sows with similar body condition were randomly allocated to five groups (n = 26), receiving basal diet (CON group) or basal diet supplemented with 0.5% IMO (IMO group), 0.5% IMO and 0.02% Bacillus subtilis (IMO+S group), 0.5% IMO and 0.02% Bacillus licheniformis (IMO+L group), and 0.5% IMO, 0.02% Bacillus subtilis and Bacillus licheniformis (IMO+S+L group), respectively. The reproductive performance of sows was recorded. During farrowing, serum of sow from the ear vein and umbilical vein were collected for determining the metabolite and antioxidatant capacity. The placenta also was collected to determine antioxidant capacity. Statistical analysis was performed with covariance analysis and one-way analysis of variance followed by a Duncan multiple range test with SPSS 21.0. The results showed that no difference was observed in litter size among all groups (P &amp;gt; 0.05), while the average piglet birth weight was improved in all treatments and the placental efficiency was increased in IMO+S group and IMO+S+L group compared with CON group (P &amp;lt; 0.05). IMO+S+L increased low-density lipoprotein cholesterol (LDL-C) and reduced total cholesterol (TC) concentration in umbilical venous serum (P &amp;lt; 0.05). In addition, sows in all treatment groups had greater malondialdehyde (MDA) levels in umbilical venous serum compared with CON group (P &amp;lt; 0.05). Total antioxidant capacity (T-AOC) of placenta was increased in IMO+L group and IMO+S+L group (P &amp;lt; 0.05). Moreover, the concentration of growth hormone (GH) in umbilical venous serum was improved (P &amp;lt; 0.05) in all treatments group. In conclusion, IMO and Bacillus supplementations during late gestation changed the lipid and protein metabolism of sows, improved the placental antioxidant capacity, increased GH levels in umbilical venous serum, ultimately improved the piglet birth weight and placental efficiency.

Could calgranulins and advanced glycated end products potentiate acromegaly pathophysiology?

Growth hormone (GH) exerts a diverse set of effects across many tissues including fat, muscle, bone, kidney, heart, and liver. GH is also a diabetogenic hormone in that it inhibits the actions of insulin. Acromegaly, a condition traditionally characterized by increased levels of growth hormone secretion as a result of pituitary adenoma, results in increased tissue growth, lipolysis, and can result in patients with hyperglycemia and hyperinsulinemia. While current treatment modalities have greatly improved prognoses for most patients, a significant number present clinical symptoms of acromegaly with elevated levels of IGF-1 in the absence of increased GH levels, a phenomenon known as micromegaly. This condition presents a challenge to most currently used treatments since the high circulating IGF-1 levels are independent of elevated levels of GH. It has been previously shown that advanced glycation end products (AGE) can stimulate IGF-1 secretion by human monocytes in vitro, demonstrating a possible mechanism for increased IGF-1 levels. To further investigate AGE/GH/IGF-1 interaction, we have reanalyzed a publicly available RNAseq dataset from subcutaneous adipose tissue of patients with acromegaly. S100A1, a member of the calgranulin family of proteins and ligand of the AGE receptor, was shown to be significantly upregulated in patients with acromegaly. These findings identify an important consideration that may help explain the counterintuitive nature of micromegaly, while simultaneously providing new insight into the role of GH in diabetic, inflammatory, and immune pathologies.