Human Growth Hormone Levels Research Articles

Genetically Modified Porcine Kidneys Have Sufficient Tissue Integrity for Use in Pig-to-Human Xenotransplantation.

We sought to determine if genetically modified porcine kidneys used for xenotransplantation had sufficient tissue integrity to support long-term function in a human recipient. Kidney transplantation remains the best available treatment for patients with end-stage kidney disease. However, a shortage of available donor human kidneys prevents many patients from achieving the benefits of transplantation. Xenotransplantation is a potential solution to this shortage. Recent pre-clinical human studies have demonstrated kidneys from genetically modified pig donors can be transplanted without hyperacute rejection and are capable of providing creatinine and other solute clearance. It is unknown whether the porcine kidneys would tolerate the relatively higher resting blood pressure in an adult human recipient compared with the pig donor or non-human primate (NHP) recipients used in translational studies. Furthermore, previous experience in NHPs raised concerns about the tissue integrity of the porcine ureter and post-xenotransplant growth of the porcine kidney. Kidneys recovered from porcine donors with 10 gene edits were transplanted into decedent brain-dead recipients who were not eligible for organ donation. Decedents underwent bilateral native nephrectomy before transplant and were followed for 3 to 7 days. Standard induction and maintenance immunosuppression was used as previously reported. Vital signs, including blood pressure, were recorded frequently. Kidney xenografts were assessed daily, serially biopsied, and were measured at implantation and study completion. Three decedents underwent successful xenotransplantation. Subcapsular hematomas developed, requiring incision of the xenograft capsules to prevent Page kidney. Blood pressures were maintained in a physiologic range for adult humans (median arterial pressures (MAP) 108.5mmHg (Interquartile Range (IQR): 97-114mmHg), 74mmHg (IQR: 71-78mmHg), and 95mmHg (IQR: 88-99mmHg, respectively) and no bleeding complications or aneurysm formation was observed. Serial biopsies were taken from the xenografts without apparent loss of tissue integrity despite the lack of a capsule. Ureteroneocystotomies remained intact without evidence of urine leak. Xenograft growth was observed, but plateaued, in 1 decedent with increased volume of the left and right xenografts by 25% and 26%, respectively, and in the context of human growth hormone levels consistently less <0.1ng/ml and insulin-like growth factor 1 levels ranging from 34-50ng/ml. The findings of this study suggest kidneys from 10-gene edited porcine donors have sufficient tissue integrity to tolerate xenotransplantation into a living human recipient. There was no evidence of anastomotic complications, and the xenografts tolerated needle biopsy without issue. Xenograft growth occurred but plateaued by the study end; further observation and investigation will be required to confirm this finding and elucidate underlying mechanisms.

Supplementation with postbiotic from Bifidobacterium Breve BB091109 improves inflammatory status and endocrine function in healthy females: a randomized, double-blind, placebo-controlled, parallel-groups study

This study evaluated the effects of dietary supplementation with a postbiotic extract of Bifidobacterium breve BB091109 on pro-inflammatory cytokines levels and markers of endocrine function. A prospective, double-blind, placebo-controlled, randomized, single-centered, parallel study was conducted on a group of 40–55-year-old females. The study included 30 healthy females, divided into two groups: a supplement (n = 20) and a placebo (n = 10) groups. Blood and saliva samples were collected at baseline (wk0), after 4 weeks (wk 4) and 12 weeks (12wk) of daily supplementation (500 mg), and 4 weeks (wk 16) after termination of supplementation. The levels of fasting CRP, IL-6, IL-10, TNF-α, IFN-γ, DHEA, estradiol, estriol, progesterone, cortisol and human growth hormone were analysed. The results revealed a significant effect of the 90-day supplementation with B. breve postbiotic extract on changes in CRP, IL-6 levels, DHEA, estradiol and estriol. In conclusion, the supplementation with the B. breve postbiotic extract improved endocrine function in females over 40 years old and induced protective changes in inflammatory markers. These findings highlight the potential health benefits of this supplementation in promoting hormonal balance and reducing inflammation in this population.

Human growth hormone, a marker for HIV infection among adult Igbo Nigerians: relationship between human growth hormone and CD4+ count with viral load.

Routine viral load and CD4+ testing is key to monitoring the extent of danger caused by HIV and response to antiretroviral therapy (ART) for HIV individuals, but its availability has been limited in low and middle-income countries. The study sort to ascertain relationship between serum Human Growth Hormone (HGH) gold standard with CD4 cells and viral load in HIV-infected patients. CD4+ T-cells, HIV viral load, and HGH were assayed in HIV- infected patients from May to December 2020. 460 subjects were engaged and separated into two groups: the HIV-infected untreated (Pre-ART) and the control groups. An interventional study was conducted for the Pre-Art group after six months. Serum HGH was assayed by the ELISA method, CD4 cell count was examined by BD-FACScan flow cytometer, and HIV viral load was assessed using RT-PCR. The CD4 count and serum HGH of Pre-ART HIV-infected subjects were significantly low (p<0.05), while the viral load was significantly high compared to those treated with ART for 6months (p<0.05). CD4 count and serum HGH were significantly higher (p<0.05) in females than in males. It also reveals that CD4 count correlates positively with HGH level (r= 0.191**). Serum HGH could serve as a surrogate marker and valuable index in monitoring HIV patients.

PMON101 Fluctuating Insulin Requirements in Untreated Acromegaly: From 200-to-0

Abstract Introduction Acromegaly is a clinical disorder that occurs from autonomous production of growth hormone (GH). Diabetic ketoacidosis (DKA) is an uncommon and late complication of acromegaly. Acromegaly presenting in DKA prognosticates glycemic management with insulin-based regimens. Cessation of insulin therapy, however, can be achieved in patients with acromegaly after proper medical and/or surgical interventions. Our case highlights a unique outcome in a patient with newly-diagnosed acromegaly that initially presented in DKA with very high insulin requirements and was ultimately de-escalated off all anti-hyperglycemic therapy with significant glycemic improvement prior to any treatment for acromegaly. Clinical Case A 32 year-old male with a past medical history of colorectal cancer and no known history of diabetes presented to the emergency department for evaluation of generalized weakness, epigastric pain, nausea, and vomiting and was admitted for DKA. Hemoglobin A1c was 11.6% (reference range &amp;lt; 5.7%), confirming the diagnosis of newly-diagnosed diabetes. C-peptide was 1.4 ng/mL (reference range 0.5-3.3 ng/mL) and anti-glutamic acid decarboxylase, anti-islet cell, and anti-zinc transporter 8 antibodies were all negative. He was initiated on intravenous insulin infusion, with rates achieving &amp;gt; 200 units of insulin per day. Given severe insulin resistance in conjunction with acromegalic features on physical exam and a unique history of colorectal cancer at a young age without any family history, evaluation for acromegaly was initiated. Human GH level was 68.60 ng/mL (reference range 0.05-3.00 ng/mL) and insulin-like growth factor-1 (IGF-1) level was 1,036 ng/mL (reference range 82-242 ng/mL). MRI brain revealed a hypoenhancing 1.3 cm lesion enlarging the left lateral pituitary gland. Diagnosis of acromegaly due to a GH-secreting macroadenoma was established. The patient was discharged on a high-dose insulin regimen in addition to metformin therapy with de-escalation off of all anti-glycemic therapy within a few weeks of diagnosis; at his 3 month follow-up visit, his repeat hemoglobin A1c was 6.1 with repeat GH level of 28.8 ng/mL and IGF-1 level of 1602 ng/mL, despite not yet undergoing any treatment for the underlying condition. Conclusion DKA as an initial presentation of acromegaly has been previously reported in literature, however, not with a concomitant history of colon cancer. Moreover, no previous cases of acromegaly have reported glycemic normalization off of anti-hyperglycemic therapy prior to any treatment for acromegaly. Our case highlights that evaluation for secondary causes, including acromegaly, should be considered in patients with severe insulin resistance and emphasizes the dramatic range of insulin requirements that patients with acromegaly may have. Presentation: Monday, June 13, 2022 12:30 p.m. - 2:30 p.m.

Maturity-Associated Variations in Resistance Exercise-Induced Hormonal Responses in Young Male Athletes

To examine differences in resistance exercise-induced hormonal responses among young athletes according to their maturity levels. A total of 12 collegiate and 32 junior high school male athletes were enrolled. The junior high school participants were divided into pre-peak height velocity (PHV) and post-PHV groups, according to their PHV ages. The salivary testosterone, cortisol, and human growth hormone levels were analyzed before (pre), immediately after (post), and at 15minutes after performing body weight resistance exercise. The testosterone levels were higher in the collegiate than in the junior high school group (P < .01) and increased after 15minutes of exercise (P < .01). A significant decrease in the cortisol levels postexercise in the junior high school groups (P < .01) and an increase in the human growth hormone levels at 15minutes after exercise in the post-PHV group were observed (P < .01). In the collegiate and post-PHV groups, the testosterone-to-cortisol ratio increased post and at 15minutes after exercise (P < .01). The testosterone-to-cortisol ratio values were higher in the collegiate than in the post-PHV (at preexercise and at 15min after [P < .01]) and pre-PHV groups (at all times [P < .01]). Exercise-induced acute hormonal responses to resistance exercise may depend on individuals' maturity levels, even in those having the same age.

Differences in somatostatin receptor subtype expression in patients with acromegaly: new directions for targeted therapy?

PurposeTo analyze the expression of somatostatin receptor (SSTR)2a and 5 by immunohistochemistry (IHC) in surgically resected somatotrophic pituitary adenomas and to associate expression rates with tumor size and clinical, biochemical, and histological parameters and response to somatostatin analog (SA) therapy.MethodsForty-three microsurgically treated patients with histopathologically proven growth hormone (GH)–producing pituitary adenoma were included (WHO 2017). SSTR subtype expression was analyzed in adenoma tissues using monoclonal antibodies (Abcam, SSTR2a-UMB1, SSTR5-UMB4). Expression rates were classified as low (≤ 20% staining positivity), moderate (21–50%), and high (> 50%). Furthermore, biochemical parameters such as human growth hormone (hGH) and insulin-like growth factor-1 (IGF-1) levels were measured and clinical, biochemical, radiological, and histological data were evaluated.ResultsOf the 43 patients included in this study, 28 were female and 15 were male. The median age was 52 years (range 17–72 years). The median tumor size was 1.2 cm (range: 0.13–3.93 cm). All resected tumors showed positivity for somatotrophic hormone (STH). In all tissue samples, SSTR2a signal expression was detectable in immunohistochemistry, while only 39 samples were positive for SSTR5. Thirty-six samples had a high expression of SSTR2a, while three had a moderate and four a low SSTR2a signal. In comparison, SSTR5 signal was high in 26 out of 43 samples, while seven adenomas showed a moderate and six cases a low expression rate of SSTR5. The median IGF-1 was 714.2 µg/l and the median GH 19.6 mU/l (= 6.53 µg/l). The present study indicates that there is no significant relationship between the expression rates of receptor subtypes and the parameters we analyzed. However, our study revealed that smaller adenomas have a lower baseline GH level (p = 0.015),ConclusionIHC with monoclonal antibodies appears to be a suitable method to determine the expression rates of SSTR2a and 5 at protein levels, as it is not possible to draw conclusions regarding receptor subtypes solely on the basis of the parameters analyzed.

Propranolol for Treatment of Infantile Hemangioma: Efficacy and Effect on Pediatric Growth and Development.

Purpose Propranolol has been successful in treating problematic infantile hemangiomas (IH) but concerns regarding its effect on normal growth and development have been raised. This study examines physical growth, developmental milestones, and human growth hormone (hGH) levels in infants receiving propranolol for problematic IH. Method Monthly heights and weights of children undergoing propranolol therapy for IH were prospectively collected and tabulated. Data analysis and comparison to World Health Organization (WHO) weight-for-age and weight-to-length z-scores was performed. Questionnaires regarding milestones, efficacy, and guardian satisfaction were performed, and a combination of both chart results and phone conducted surveys was tabulated. Serum from a small representative cohort of age-matched children with IH treated and not treated with propranolol was collected. Results A total of 185 children receiving propranolol therapy between 2008 and 2013 for IH were assigned to this study. The children were divided into two cohorts based on the presence of comorbidities or risk factors that may affect growth and development (n = 142 no comorbidities, n = 43 with comorbidities). Neither cohort demonstrated deviation from normal weight in comparison to WHO normative data. There was a significant deviation for BMI-for-age and weight-for-age z-scores in our population, especially in patients on propranolol for more than 7 months. Based on data from participants, via either completed questionnaires or chart results, most children met their developmental milestones at or before target ages, regardless of the presence of comorbidities. Eighty percent of guardians noticed clinical improvement of the IH, with 91% either happy about or neutral to using the medication. hGH levels were higher in patients receiving propranolol therapy, but not significantly different. Conclusion Propranolol therapy is effective and well tolerated in the treatment of infantile hemangiomas. This study suggests that propranolol does not impair growth and has no impact on normal pediatric development.

Dexamethasone Rescues an Acute High-Fat Diet-Induced Decrease in Human Growth Hormone Gene Expression in Male Partially Humanized CD-1 Mice.

Obesity in puberty, already a time of insulin resistance, increases the risk of developing type 2 diabetes. Human (h) growth hormone (GH) levels also peak during puberty, where it contributes to growth and energy homeostasis through positive effects on maintaining pancreatic β cell mass. Thus, it is important to understand the effects of overeating and obesity on hGH production in puberty. Three days of overeating in young male adults or high-fat diet (HFD) in pubescent male transgenic (171hGH/CS) CD-1 mice containing the hGH gene (hGH-N) results in excess insulin and a decrease in hGH production. This reduction in these mice occurred during the light phase of the daily cycle, and was associated with decreased availability of the clock-related transcription factor Brain and Muscle ARNT-Like 1 (Bmal1). However, the HFD-induced decrease in hGH-N expression was blocked by forced daily swim activity, which is expected to increase glucocorticoid (GC) levels. The aim of the study was to assess whether GCs, specifically daily injections with a pharmacological dose of dexamethasone (DEX) in the light or dark phase of the daily cycle, can limit the negative effect of HFD for 3 days on hGH-N expression in male 171hGH/CS mice. DEX treatment increased or rescued hGH-N RNA levels, and was associated with elevated Bmal1 transcripts when assessed 12 h after final treatment, and at a time when serum corticosterone levels were suppressed >90%. In addition, a diet-dependent effect on hGH-N RNA levels was observed at 36 h after final treatment, but only in the light stage, presumably due to residual effects of DEX treatment and/or recovery of endogenous corticosterone levels. This is the first evidence for a direct effect of GCs on hGH-N expression in vivo and the ability to potentially limit the negative effect of overeating/obesity on hGH production in puberty.

Measuring IGF-1 and IGFBP-3 profiles in women seeking assisted reproduction; relationship to serum growth hormone levels (Study 3)

Extending from our first two studies examining the IGF profile (IGF-1, IGFBP-3 and the ratio of IGFBP-3/ IGF-1) in women presenting for assisted reproductive technologies (ART), this study examines its relevance to the testing of human growth hormone (hGH) levels on the same blood sample. These were taken in the morning during the early follicular phase of the woman’s menstrual cycle and included 408 women who were ART-naïve, undertaking the tests as part of an assessment cycle prior to any ART treatment. The growth hormone levels were also tested on a further 945 women classified as ART-interval cases. It was shown that the vast majority of hGH levels (73%) were very low at &lt;1.0 ng/mL and 22% are extremely low &lt;0.1 ng/mL, close to the detection level of the chemiluminescent immunoassay (0.03 ng/mL). Only 12% of hGH levels were recorded in the range ≥3.0 ng/mL, levels which exclude adult growth hormone deficiency (AGHD). Although IGF-1 levels are regarded as a screening test for AGHD, our studies showed no correlation between hGH levels and the entire range of IGF-1 levels, neither across IGFBP-3 levels, nor across IGF Ratios, albeit there was an apparent inverse trend for the latter. Across the entire age range, the hGH levels were not statistically different among neither the ART-naïve nor the ART-interval women. Furthermore, hGH levels were not different among the clinical parameters of stature or BMI; nor for ovarian reserve parameters AMH or AFC. It is concluded that serum hGH screening probably has very limited value as a screening test for potential AGHD.

Mechanism for the Increase in Human Growth Hormone with Administration of a Novel Test Supplement and Results Indicating Improved Physical Fitness and Sleep Efficiency.

An oral test supplement increases serum human growth hormone (hGH) levels after acute administration in healthy adults. We investigated the mechanism for the increase in hGH and the effect of continued daily administration of the test supplement on measures of physical fitness and sleep efficiency. In Study 1, serum triiodothyronine (T3) was measured in samples from a prior placebo-controlled, double-blind study in which 16 healthy participants received both placebo and the test supplement in a crossover design; treatment order was randomized, and treatments were separated by a 1-week washout. In Study 2, physical fitness (VO2 max) was measured at baseline and after 2 weeks of daily administration of the test supplement (N = 12 healthy participants). Study 3 assessed daily sleep onset latency and time awake during 3 weeks of daily administration of the test supplement (N = 15 healthy participants). A fall from baseline in T3 was observed with placebo (-6.1 ± 8.5 ng/dL, P = .01). Of note, the change in T3 was smaller with the test supplement (-3.3 ± 10.7 ng/dL, P = not significant) but was not statistically different from placebo. Mean VO2 max increased by 6% from baseline after 2 weeks (P = .02). Sleep-onset latency and time awake during the night were reduced from baseline to week 3 by 22% and 65%, respectively (P = .01 and P = .02). The conservation of T3 levels suggests that the mechanism for increased hGH secretion by the test supplement is through somatostatin inhibition. Furthermore, pilot studies indicated that daily administration of the supplement improved physical fitness and sleep efficiency from baseline, effects consistent with increased endogenous hGH release. Clinical Trial Registration No. NCT02987868.

Human growth hormone level decreased in women aged 50 years.

To investigate the relationship amongst human growth hormone (HGH), sex, and age groups.A cross-sectional study was conducted on a health check-up population from Wannan area of China from 2014 to 2016. The study involved 6843 individuals aged 23 to 85 years. Logistic regression analysis and smooth curve were applied to determine the relationship amongst age, sex, and HGH.The average level of HGH in the population was 0.37 ± 0.59 ng/mL. There were significant differences in sex, age, body mass index (BMI), triglycerides (TG), total cholesterol (TC), systolic blood pressure (SBP), diastolic blood pressure (DBP), and glucose (GLU) amongst different quartiles of HGH (P < .001). A U-shape relationship was established between HGH and age. After sex stratification, the results showed that the thresholds of age were 60 years in women, and 50 years in men, after adjusting for body mass index, triglycerides, total cholesterol, blood pressure, and blood glucose. Logistic regression showed that HGH level decreased in women aged <60 years (OR = 1.472, P < .001) and increased in men aged >50 years (OR = 0.711, P < .001). So the distributive characteristics of HGH concentration vary with sex and age group.

Glucose Counter-regulation After Acute Pancreatitis.

Persistent hyperglycemia is a common sequela of acute pancreatitis (AP). The role of counter-regulatory hormones in maintaining glucose homeostasis has been largely studied during the course of AP, but not after clinical resolution of the disease. The objectives of this study were to investigate the associations between circulating levels of glucagon, cortisol, and human growth hormone and glucose homeostasis after AP as well as their associations with a comprehensive panel of pancreatic hormones, gut peptides, and proinflammatory cytokines. Participants with no history of pre-existing prediabetes or diabetes were categorized into hyperglycemia and normoglycemia after AP groups. Binary logistic regression and linear regression analyses were conducted. Eighty-three individuals were included, of whom 19 had hyperglycemia. Glucagon, cortisol, and human growth hormone did not differ significantly between the groups. Glucagon explained up to 86% of the variance in glucagon-like peptide 1, whereas cortisol explained up to 89% of the variance in interleukin 6 in hyperglycemia after AP. Counter-regulatory hormones do not appear to play a direct role in the mechanisms underlying hyperglycemia after AP. However, significant associations between glucagon and glucagon-like peptide 1, as well as between cortisol and interleukin 6, suggest that that these hormones may be involved indirectly in the pathophysiology of hyperglycemia after AP.

Hormonal responses to striking combat sports competition: a systematic review and meta-analysis.

Striking combat sports are challenging, commonly stressing the endocrinological system based on a mixture of body-contact actions and physiological efforts. The aims of this systematic review and meta-analysis were to discuss the hormonal responses related to striking combat sports competitions and to investigate the moderator and mediator variables of the hormonal response-competition/outcome relationship. Three electronic databases (i.e., PubMed, Google Scholar and ScienceDirect) were systematically searched (up to February 2016) followed by a manual search of retrieved papers. The data showed a moderate increase in cortisol (C) (ES = 0.79; 95% CI 0.31–1.28; p = 0.001), an extremely large increase in adrenaline (ES = 4.22; 95% CI 2.62–5.82; p < 0.001), and a very large increase in noradrenaline (ES = 3.40; 95% CI 1.03–5.76; p = 0.005) and human growth hormone (HGH) levels (ES = 3.69; 95% CI 1.96–5.42; p < 0.001) immediately following the combat events, compared to the control condition i.e., “pre-combat”. Furthermore, amateur athletes had a larger increase in C levels compared to highly trained athletes (ES = 2.91 [very large] vs ES = 0.56 [small]), while evening events showed greater alterations in C levels compared to morning events (ES = 1.91 [large] vs ES = 0.48 [small]), without significant differences between them (p = 0.26 and p = 0.06, respectively). The present meta-analysis also showed a small, insignificant increase in testosterone (T) (ES = 0.47 [small]; 95% CI -0.45–0.99; p = 0.074) and a decrease in insulin-like growth factor 1 levels (ES = -0.20 [trivial]; 95% CI -0.78–0.37; p = 0.486) immediately following the combat events, compared to the control condition. The type of combat sports practised, participants’ gender, and the nature of competition contests (i.e., official vs simulation) did not moderate the relationship between competition and hormonal response. Additionaly, sub-analysis results showed a significant difference between younger and older athletes (Q = 4.05, p = 0.044), suggesting that after combat, younger individuals (less than 17 years of age) had a small decrease in T levels (ES = -0.58), compared with the moderate increase observed in older individuals (ES = 0.76). In conclusion, irrespective of striking combat sports types, the results showed that both official and simulated bouts are a real stressor of the hormonal system of practitioners. Coaches and applied practitioners should adopt “pre-competitive cognitive/coping strategies” to improve the psychological state that mediates the hormonal changes-competition/outcome relationship of their athletes in order to mitigate athletes’ stress.

Surgical debulking of pituitary adenomas improves responsiveness to octreotide lar in the treatment of acromegaly.

Studies comparing primary medical treatment of acromegaly with surgery are often non-randomized, and not stratified by illness severity. We prospectively compared primary medical therapy with pituitary surgery in patients with acromegaly. All patients had macroadenomas, at least one random human growth hormone (GH) level ≥12.5ng/mL, elevated IGF-I levels and failure to suppress GH to <1ng/mL during an oral glucose tolerance test (oGTT). Forty-one patients from seven centers were randomized to primary treatment with octreotide LAR, 30mg every 4 weeks × 3 months (ARM A, N = 15), or pituitary surgery (ARM B, N = 26) using a 1:2 randomization design. Patients cured by surgery (defined as nadir GH during oGTT <1ng/mL and normal IGF-I) received no subsequent treatment. Those not cured surgically were then treated with octreotide LAR (SubArm B1) for 3 months. Only one of the 15 patients in ARM A (6.7%) had normalization of both GH and IGF-I. In contrast, 13/26 patients had normalization of both GH and IGF-I after surgery alone (50%). Of the remaining 13 patients who did not normalize with surgery alone, treatment with octreotide LAR resulted in a normal nadir GH and normal serum IGF-I in 7 (53.9%). In total, 20/26 in ARM B (76.9%) experienced normalization of defined biochemical acromegaly parameters. Pituitary surgery alone was more effective than primary medical treatment (p = 0.006), and the combination of surgery followed by medical therapy was even more effective (p < 0.0001). Subjects treated with medical therapy after surgical debulking had a significant improvement in response rate compared to matched subjects treated with primary medical therapy.

Exploiting Nanobodies in the Detection and Quantification of Human Growth Hormone via Phage-Sandwich Enzyme-Linked Immunosorbent Assay

Monitoring blood levels of human growth hormone (hGH) in most children with short stature deficiencies is crucial for taking a decision of treatment with extended course of daily and expensive doses of recombinant hGH (rhGH or Somatropin®). Besides, misusing of rhGH by sportsmen is banned by the World Anti-Doping Agency and thus sensitive GH-detecting methods are highly welcome in this field. Nanobodies are the tiniest antigen-binding entity derived from camel heavy chain antibodies. They were successfully generated against numerous antigens including hormones. A fully nanobody-based sandwich ELISA method was developed in this work for direct measurement of GH in biological samples. Two major characteristics of nanobody were exploited for this goal: the robust and stable structure of the nanobody (NbGH04) used to capture hGH from tested samples, and the great ability of tailoring, enabling the display of the anti-GH detector nanobody (NbGH07) on the tip of M13-phage. Such huge, stable, and easy-to-prepare phage-Nb was used in ELISA to provide an amplified signal. Previously, NbGH04 was retrieved on immobilized hGH by phage display from a wide "immune" cDNA library prepared from a hGH-immunized camel. Here, and in order to assure epitope heterogeneity, NbGH07 was isolated from the same library using NbGH04-captured hGH as bait. Interaction of both nanobodies with hGH was characterized and compared with different anti-GH nanobodies and antibodies. The sensitivity (~0.5 ng/ml) and stability of the nanobody-base sandwich ELISA were assessed using rhGH before testing in the quantification of hGH in blood sera and cell culture supernatants. In regard to all advantages of nanobodies; stability, solubility, production affordability in Escherichia coli, and gene tailoring, nanobody-based phage sandwich ELISA developed here would provide a valuable method for hGH detection and quantification.

Approach to growth hormone therapy in children with chronic kidney disease varies across North America: the Midwest Pediatric Nephrology Consortium report

BackgroundGrowth impairment remains common in children with chronic kidney disease (CKD). Available literature indicates low level of recombinant human growth hormone (rhGH) utilization in short children with CKD. Despite efforts at consensus guidelines, lack of high-level evidence continues to complicate rhGH therapy decision-making and the level of practice variability in rhGH treatment by pediatric nephrologists is unknown.MethodsCross-sectional online survey electronically distributed to pediatric nephrologists through the Midwest Pediatric Nephrology Consortium and American Society of Pediatric Nephrology.ResultsSeventy three pediatric nephrologists completed the survey. While the majority (52.1%) rarely involve endocrinology in rhGH management, 26.8% reported that endocrinology managed most aspects of rhGH treatment in their centers. The majority of centers (68.5%) have a dedicated renal dietitian, but 20.6% reported the nephrologist as the primary source of nutritional support for children with CKD. Children with growth failure did not receive rhGH most commonly because of family refusal. Differences in initial work-up for rhGH therapy include variable use of bone age (95%), thyroid function (58%), insulin-like growth factor-1 (40%), hip/knee X-ray (36%), and ophthalmologic evaluation (7%). Most pediatric nephrologists (95%) believe that rhGH treatment improves quality of life, but only 24% believe that it improves physical function; 44% indicated that rhGH improves lean body mass.ConclusionsThere is substantial variation in pediatric nephrology practice in addressing short stature and rhGH utilization in children with CKD. Hence, there may be opportunities to standardize care to study and improve growth outcomes in short children with CKD.

Inorganic Nitrate Mimics Exercise-Stimulated Muscular Fiber-Type Switching and Myokine and γ-Aminobutyric Acid Release.

Exercise is an effective intervention for the prevention and treatment of type 2 diabetes. Skeletal muscle combines multiple signals that contribute to the beneficial effects of exercise on cardiometabolic health. Inorganic nitrate increases exercise efficiency, tolerance, and performance. The transcriptional regulator peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) coordinates the exercise-stimulated skeletal muscle fiber-type switch from glycolytic fast-twitch (type IIb) to oxidative slow-twitch (type I) and intermediate (type IIa) fibers, an effect reversed in insulin resistance and diabetes. We found that nitrate induces PGC1α expression and a switch toward type I and IIa fibers in rat muscle and myotubes in vitro. Nitrate induces the release of exercise/PGC1α-dependent myokine FNDC5/irisin and β-aminoisobutyric acid from myotubes and muscle in rats and humans. Both exercise and nitrate stimulated PGC1α-mediated γ-aminobutyric acid (GABA) secretion from muscle. Circulating GABA concentrations were increased in exercising mice and nitrate-treated rats and humans; thus, GABA may function as an exercise/PGC1α-mediated myokine-like small molecule. Moreover, nitrate increased circulating growth hormone levels in humans and rodents. Nitrate induces physiological responses that mimic exercise training and may underlie the beneficial effects of this metabolite on exercise and cardiometabolic health.

The Influence of Physical Training on Blood Levels of Human Growth Hormone, Testosterone and Procollagen in Young Rowers

Objective : The purpose of this study was to investigate muscle strength and skeletal age in trained and untrained pubertal boys and its relationship to the levels of Testosterone (T), Growth Hormone (GH) and Procollagen (PICP). Methods : Both the exercise and control groups consisted of 24 (mean 12.91, sd = 0.63) and 17 (mean 12.91, sd = 0.48) year old boys, respectively. The exercise group (EG), in addition to school activities, participated in a rowing training program for six months (rowing technique, strength & aerobic exercises, 60 min/day, three days/week). The control group (CG) only participated in the school physical education program, two to three times/week. Hormonal concentrations were measured by radioimmunoassay techniques. Venus blood samples were taken at rest from both groups. Results : Testosterone was increased in both groups (p<0.001). Significant differences were found within groups in T before training (p<0.01) There was an increase of PICP in EG after training (p<0.01). Differences on GH were observed before the training period in both groups (p<0.01). Both groups significantly differed in upper and lower limbs strengths. Significant correlation was found between PICP and skeletal age in both (p<0.05 and p<0.02, respectively) Conclusions: The gains in muscle strength in both groups may partly be explained by the increase in the concentrations of hormone levels and the changes in body size. Key words : skeletal age, muscle strength, anabolic hormones, rowing

Optimizing conditions for production of high levels of soluble recombinant human growth hormone using Taguchi method

Human growth hormone (hGH) is synthesized and stored by somatotroph cells of the anterior pituitary gland and can effect on body metabolism. This protein can be used to treat hGH deficiency, Prader–Willi syndrome and Turner syndrome. The limitations in current technology for soluble recombinant protein production, such as inclusion body formation, decrease its usage for therapeutic purposes. To achieve high levels of soluble form of recombinant human growth hormone (rhGH) we used suitable host strain, appropriate induction temperature, induction time and culture media composition. For this purpose, 32 experiments were designed using Taguchi method and the levels of produced proteins in all 32 experiments were evaluated primarily by ELISA and dot blotting and finally the purified rhGH protein products assessed by SDS–PAGE and Western blotting techniques. Our results indicate that media, bacterial strains, temperature and induction time have significant effects on the production of rhGH. The low cultivation temperature of 25°C, TB media (with 3% ethanol and 0.6M glycerol), Origami strain and a 10-h induction time increased the solubility of human growth hormone.

Effect of GenF20 Plus on serum IGF-1 levels in healthy adults: a randomized controlled study

Effect of GenF20 Plus on serum IGF-1 levels in healthy adults: a randomized controlled study Navneet Sonawane,1 Vinayak Kale,2 Suhas Erande,3 Jayesh Chaudhary1 1Vedic Lifesciences Pvt Ltd, Mumbai, India; 2Lokmanya Hospital, Pune, India; 3Akshay Hospital, Pune, India Background: Aging is related to a reduction of growth hormones, resulting in physiological derailment and affects overall wellbeing. GenF20 Plus is a dietary supplement postulated to naturally stimulate the secretion of human growth hormone (HGH) through the anterior pituitary. This study sought to evaluate the effect of GenF20 Plus in enhancing the levels of insulin-like growth factor-1 (IGF-1), which is a marker of HGH levels. Methods: Seventy subjects aged 35&ndash;65 years visiting outpatient departments at five study centers across India, presenting with at least two of the following age-related complaints: decreased memory, decreased libido, low energy levels, or poor quality of sleep were randomly assigned to either GenF20 Plus (n=35) or placebo (n=35) for a period of 12 weeks (84 days). Randomization was carried out using computerized software. The primary outcome measure was serum IGF-1 levels. Changes in waist circumference, body mass index, body fat percentage, lean muscle mass, and scores for memory, libido, energy levels, and quality of sleep were also assessed. Trial registration: CTRI/2011/06/001784. Results: Sixty-one subjects completed the study as per protocol and were analyzed. The mean increase (mean &plusmn; standard deviation) in IGF-1 levels at day 84 in the GenF20 Plus group was 13.46&plusmn;36.12 ng/mL and in the placebo group was 6.35&plusmn;36.56 ng/mL, which was not statistically significantly different (P&gt;0.05) when compared across the groups. In the &ge;40 years subgroup, the mean increase in IGF-1 in the GenF20 Plus group (14.59&plusmn;40.08 ng/mL) was not statistically significantly different when compared to the placebo group (3.17&plusmn;16.09 ng/mL) using analysis of variance (ANOVA; P&gt;0.05). However, when this change was analyzed using analysis of covariance (ANCOVA) considering baseline values as the covariates, it was found to be statistically significantly different (GenF20 Plus: 22.69&plusmn;40.62 ng/mL, placebo: -4.31&plusmn;16.79 ng/mL; P&lt;0.05). The changes in IGF-1 values in the &lt;40 years subgroup were not found to be statistically significant. No statistically significant difference over placebo was seen for the other variables. Conclusion: GenF20 Plus increased serum IGF-1 levels in subjects &ge;40 years of age who physiologically have reduced IGF-1 levels. However, significant changes in other parameters were not seen, probably due to the short duration of treatment. Further studies with longer treatment duration and large sample size are warranted to understand the clinical benefits of GenF20 Plus, especially in adults above 40 years of age. Keywords: IGF-1, herbal supplement, human growth hormone, HGH, aging&nbsp;