Stimulates Growth Hormone Secretion Research Articles

Micronutrients in Adverse Pregnancy Outcomes

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or “adverse pregnancy” associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance, structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

Growth hormone treatment for neurologic symptoms of post-acute sequelae of COVID-19.

Following SARS-CoV-2 infection, some patients develop lingering neurologic symptoms of post-acute sequelae of COVID-19 (PASC) that commonly include fatigue and "brain fog." PASC symptoms are also linked with reduced growth hormone (GH) secretion, but GH treatment has not been tested to relieve symptoms. We enrolled 13 adults with neurologic PASC symptoms and peak stimulated GH secretion less than 10 ng/mL (glucagon stimulation) in a pilot study to receive 9 months of daily GH injections and an additional 3 months of off-treatment assessment. We compared peak stimulated GH secretion at baseline and 12 months and assessed measures of cognition, metabolism, body composition, and physical performance over the first 6 months of treatment. Patient-reported outcomes of fatigue, quality of life, sleep, and mood were recorded at baseline and compared with timepoints at 6, 9, and 12 months. GH treatment was associated with significantly improved scores for Brief Fatigue Inventory, Multidimensional Fatigue Symptom Inventory, Quality of Life Assessment of GrowthHormone Deficiency in Adults, Profile of Mood States, and Beck Depression Inventory-II, with no significant change in Pittsburgh Sleep Quality Index. Six months of adjunct GH treatment was not associated with significant changes in cognition, body composition, resting energy expenditure, or physical performance. Peak stimulated GH secretion was not altered at 12 months following 9 months of GH treatment. GH treatment significantly improved neurologic symptoms in PASC patients but cognition, sleep, and physical performance were not significantly altered.

Oral SSTR5 Antagonist SCO-240 for Growth Hormone Stimulation: A Phase I Single-Dose Study in Healthy Individuals.

Somatostatin inhibits endocrine and exocrine secretion in various tissues by acting on five somatostatin receptor subtypes (SSTR1-5). The clinical effects of SSTR5 antagonism remain unknown. Herein, we evaluated the effects of SCO-240, an oral SSTR5 antagonist, in healthy individuals. This randomized, single-center, double-blind, placebo-controlled, phase I study included healthy Japanese and White individuals. The effects of ascending single oral doses of SCO-240 were evaluated in healthy individuals. The main outcome measures were safety, tolerability, pharmacokinetics, and pharmacodynamics (gallbladder contractions and levels of serum insulin and plasma glucagon-like peptide-1 (GLP-1)). The levels of pituitary hormones were evaluated in our exploratory analysis. The results indicated that SCO-240 was safe and well-tolerated at all tested doses. Oral SCO-240 was readily absorbed, with its systemic exposure increasing in a dose-dependent manner. The median time to maximum concentration and mean terminal half-life of SCO-240 were 3-4 and 10.2-12.6 hours, respectively, in the ascending dose section. No clinically meaningful changes in SCO-240 pharmacokinetic profiles were observed between fed and fasted or between Japanese and White individuals. No increase in gallbladder contractions or levels of insulin and GLP-1 were detected. SCO-240 induced robust growth hormone (GH) secretion without altering the levels of other pituitary hormones. In conclusion, the study is the first to demonstrate that SSTR5 antagonism stimulates GH secretion in humans. SCO-240 was safe and well-tolerated and exhibited once-daily oral dosing potential. The robust effects of SCO-240 on GH secretion suggest that it may be a treatment option for GH-related disorders.

Micronutrients in Adverse Pregnancy Outcomes.

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or "adverse pregnancy" associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance, structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

Micronutrients in Adverse Pregnancy Outcomes

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or “adverse pregnancy” associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance a structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

Promotion of longitudinal bone growth by the intake of oat and green onion root water extracts in weaning rats through stimulating growth hormone secretion and elevating gut microbiota related to nervous system-related pathway

We determined whether oral oat and green onion water extracts (GOO) supplementation could stimulate longitudinal bone growth in weaning rats. Fistuloside A, B, and C in the green onions and 26-desglucoavenacoside A and B and avenacoside A in the oats lowered the binding energy of growth differentiation factor-5 (GDF5) and insulin-like growth factor-1 receptor (IGF1R). After a 4-week treatment, serum growth hormone (GH) and osteoprotegerin concentrations in the High-GOO group (500 mg/kg body weight) were similar to those of the Positive-control. The femur and tibia lengths promoting the proliferative and hypertrophic zones of the growth plate in the High-GOO were also similar to Positive-control. Along with increasing serum propionate and butyrate concentrations, cecal bacteria in the High-GOO were higher in virus infection, steroid and sesquiterpenoid biosynthesis, and nervous system-related pathways than the Control in the metagenome function. It suggested that gut bacteria potentially enhanced bone growth by improving immunity and neurological activity. In conclusion, GOO increased leg length by enhancing the proliferation of the growth plate as much as GH treatment by preventing gut dysbiosis.

Micronutrients in Adverse Pregnancy Outcomes

About 10 to 20% of reported pregnancies have complications like spontaneous abortion (SA), preeclampsia (PE), preterm birth (PTB), and fetal growth restriction (FGR); 60% are attributed to maternal nutritional alterations. Multiple micronutrients (MMN) are supplemented in the antenatal period, but no proper validation/guidelines are available regarding dosing/time, the need for initiation, and the duration of supplementation. Studies have reported adverse pregnancy complications related to the overuse/unwanted use of multiple micronutrient supplementations during pregnancy. Identifying the exact population requiring supplementation is necessary to prevent its abuse. This article attempts to review the impacts of micronutrient deficiency/supplementation in cases of SA, FGR, and gestational diabetes mellitus (GDM), preterm delivery and PE. The study used a literature search using PubMed, Google Scholar, Mendeley, and Scopus Databases using search words pregnancy, spontaneous abortion, gestational diabetes mellitus (GDM), fetal growth restriction (FGR), preterm delivery, preeclampsia (PE) or “adverse pregnancy” associated with minerals, micronutrients, or supplementation. The review also considered in-house literature databases, a single-window search at Kasturba Medical College (KMC) Health sciences library, MAHE (Manipal Academy of Higher Education). The figures included in the study were created by Biorender.com. Micronutrients play multiple roles during pregnancy and fetoplacental growth stimulating growth hormone secretion, Lysyl oxidase (LOX), involved in the crosslinking between collagen and elastin in the amniotic membrane, downregulation of interleukin (IL)-1 alpha, IL-1 beta, IL-4, IL-6, Il-10, IL-12, tumor necrosis factor (TNF)-alpha and several chemokines involved in hypertension, immune-inflammatory pathways, attenuate insulin resistance a structural development of neurons and glia. Over-supplementation has led to complications such as spontaneous abortion and gestational diabetes mellitus. Since there is a lack of standardization concerning micronutrient supplementation during pregnancy, there is a need for systematic study related to the role of micronutrients during each trimester of pregnancy to optimize its supplementation and to prevent hazards associated with its abuse.

Inclusion and Withdrawal Criteria for Growth Hormone (GH) Therapy in Children with Idiopathic GH Deficiency—Towards Following the Evidence but Still with Unresolved Problems

According to current guidelines, growth hormone (GH) therapy is strongly recommended in children and adolescents with GH deficiency (GHD) in order to accelerate growth rate and attain normal adult height. The diagnosis of GHD requires demonstration of decreased GH secretion in stimulation tests, below the established threshold value. Currently, GHD in children is classified as secondary insulin-like growth factor-1 (IGF-1) deficiency. Most children diagnosed with isolated GHD present with normal GH secretion at the attainment of near-final height or even in mid-puberty. The most important clinical problems, related to the diagnosis of isolated GHD in children and to optimal duration of rhGH therapy include: arbitrary definition of subnormal GH peak in stimulation tests, disregarding factors influencing GH secretion, insufficient diagnostic accuracy and poor reproducibility of GH stimulation tests, discrepancies between spontaneous and stimulated GH secretion, clinical entity of neurosecretory dysfunction, discrepancies between IGF-1 concentrations and results of GH stimulation tests, significance of IGF-1 deficiency for the diagnosis of GHD, and a need for validation IGF-1 reference ranges. Many of these issues have remained unresolved for 25 years or even longer. It seems that finding solutions to them should optimize diagnostics and therapy of children with short stature.

Protective and Healing Effects of Ghrelin and Risk of Cancer in the Digestive System.

Ghrelin is an endogenous ligand for the ghrelin receptor, previously known as the growth hormone secretagogue receptor. This hormone is mainly produced by endocrine cells present in the gastric mucosa. The ghrelin-producing cells are also present in other organs of the body, mainly in the digestive system, but in much smaller amount. Ghrelin exhibits a broad spectrum of physiological effects, such as stimulation of growth hormone secretion, gastric secretion, gastrointestinal motility, and food intake, as well as regulation of glucose homeostasis and bone formation, and inhibition of inflammatory processes. This review summarizes the recent findings concerning animal and human data showing protective and therapeutic effects of ghrelin in the gut, and also presents the role of growth hormone and insulin-like growth factor-1 in these effects. In addition, the current data on the possible influence of ghrelin on the carcinogenesis, its importance in predicting the risk of developing gastrointestinal malignances, as well as the potential usefulness of ghrelin in the treatment of cancer, have been presented.

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.

Growth hormone treatment for short stature associated with duplication of the NSD1 Sotos syndrome gene

SummaryNSD1 deletions are associated with the Sotos syndrome, a syndrome of overgrowth in childhood without evidence of endocrine disturbance. Duplications involving the NSD1 gene have been reported to be associated with a ‘reverse Sotos syndrome’ phenotype, characterised by short stature, microcephaly, dysmorphic features and developmental delay. A 2-year-old girl with short stature, dysmorphic features and developmental delay was found to have duplication of 5q32.2–5q32.3, which includes the NSD1 gene. Growth hormone stimulation testing was normal. Growth hormone therapy was initiated at 5 years of age due to severe short stature and growth failure, with height 3.35 standard deviations (SDS) below the median. Growth velocity increased markedly, by +4.91 SDS in the first year of treatment. At the time of last follow-up at 9 years and 11 months, she had achieved a height within 1 SDS of the median. This is the first report of growth hormone therapy for the short stature associated with duplication of the NSD1 gene, showing that despite normal pituitary function, exogenous growth hormone can dramatically improve linear growth.Learning pointsSotos syndrome is a disorder of childhood overgrowth caused by NSD1 deletions.Duplications involving NSD1 cause a ‘reverse Sotos syndrome’ phenotype characterised by short stature and microcephaly.The contrasting phenotypes of NSD1 deletions and duplications suggest a dose effect.Stimulated growth hormone secretion is normal in children with NSD1 deletions and duplications.Growth hormone therapy can be very effective in children with NSD1 duplications, comparable to the response seen in severe growth hormone deficiency.

Identification and Optimization of Pyrrolidine Derivatives as Highly Potent Ghrelin Receptor Full Agonists.

Muscle atrophy and cachexia are common comorbidities among patients suffering from cancer, chronic obstructive pulmonary disease, and several other chronic diseases. The peptide hormone ghrelin exerts pleiotropic effects including the stimulation of growth hormone secretion and subsequent increase of insulin-like growth factor-1 levels, an important mediator of muscle growth and repair. Ghrelin also acts on inflammation, appetite, and adipogenesis and therefore has been considered a promising therapeutic target for catabolic conditions. We previously reported on the synthesis and properties of an indane based series of ghrelin receptor full agonists which led to a sustained increase of insulin-like growth factor-1 in a dog pharmacodynamic study. Herein we report on the identification of a series of pyrrolidine or piperidine based full agonists and attempted optimization to give compounds with profiles suitable for progression as clinical candidates.

MON-603 GPR142 Expression Levels Were Correlated with Plasma Ghrelin Levels and Heights in Morbidly Obese Patients

Recently, aromatic amino acids, especially tryptophan were discovered to be the strongest ligands for GPR142, which was previously known as an orphan GPCR. GPR142 is expressed in the digestive tract and pancreas in mice and human. Previously we found that GPR142 is highly expressed in the ghrelin-producing cell line, MGN3-1 cells, and that tryptophan strongly stimulated ghrelin secretion in vitro.In this study, we measured the mRNA expression levels of GPR142 in the gastric samples of 6 morbid obese patients undergone laparoscopic sleeve gastrectomy and compared its level with their clinical parameters. GPR142 expression levels were negatively correlated with plasma desacyl ghrelin levels (p=0.011) and positively correlated with heights (p=0.08).The current results that GPR142 expression levels were correlated with plasma desacyl ghrelin levels may confirm the link between GPR142 signal and regulation of ghrelin secretion demonstrated in our in vitro study. Regarding to the correlation with heights, there are some reports that plasma ghrelin levels were inversely correlated with heights in children[1-3], although, as far as we know, there are no reports demonstrating the relationship between plasma ghrelin levels and heights in adults. Considering that ghrelin strongly stimulates growth hormone secretion, GPR142 signaling may have influence on height through regulating ghrelin-growth hormone axis.ConclusionGPR142 mRNA expression levels were negatively and positively correlated with plasma desacyl ghrelin levels and heights in morbid obese adults undergone bariatric surgery. Current results may help understanding the pathophysiological role of GPR142 in the regulation of ghrelin secretion and heights.

Abundant expression of the membrane-anchored protease-regulator RECK in the anterior pituitary gland and its implication in the growth hormone/insulin-like growth factor 1 axis in mice

The tumor suppressor gene Reversion-inducing cysteine-rich protein with Kazal motifs (Reck) encodes a membrane-anchored protease regulator expressed in multiple tissues in mouse embryos and is essential for embryonic development. In postnatal mice, however, physiological roles for the RECK protein remain unclear. We found in this study that Reck is abundantly expressed in growth hormone (GH)-producing cells (somatotrophs) in the anterior pituitary gland (AP). We also found that two types of viable Reck mutant mice, one with reduced RECK expression (Hypo mice) and the other with induced Reck deficiency from 10 days after birth (iKO mice treated with tamoxifen), exhibit common phenotypes including decreases in body size and plasma levels of insulin-like growth factor-1 (IGF1). To gain insights into the function of RECK in the AP, we characterized several somatotroph-associated molecules in the AP of these mice. Immunoreactivity of GH was greatly reduced in tamoxifen-treated iKO mice; in these mice, two membrane receptors involved in the stimulation of GH secretion [growth hormone secretagogue receptor (GHSR) and growth hormone releasing hormone receptor (GHRHR)] were decreased, however, their mRNAs were increased. Decrease in GHSR immunoreactivity and concomitant increase in its mRNA were also found in the other mutant line, Hypo. Furthermore, reduced immunoreactivity of growth hormone receptor (GHR) and concomitant increase in its mRNA was also found in the liver of Hypo mice. These results raise the possibility that RECK supports proper functioning of the GH/IGF1 axis in mice, thereby affecting their growth and metabolism.

Model informed quantification of the feed-forward stimulation of growth hormone by growth hormone-releasing hormone.

AimsGrowth hormone (GH) secretion is pulsatile and secretion varies highly between individuals. To understand and ultimately predict GH secretion, it is important to first delineate and quantify the interaction and variability in the biological processes underlying stimulated GH secretion. This study reports on the development of a population nonlinear mixed effects model for GH stimulation, incorporating individual GH kinetics and the stimulation of GH by GH‐releasing hormone (GHRH).MethodsLiterature data on the systemic circulation, the median eminence, and the anterior pituitary were included as system parameters in the model. Population parameters were estimated on data from 8 healthy normal weight and 16 obese women who received a 33 μg recombinant human GH dose. The next day, a bolus injection of 100 μg GHRH was given to stimulate GH secretion.ResultsThe GH kinetics were best described with the addition of 2 distribution compartments with a bodyweight dependent clearance (increasing linearly from 24.7 L/h for a 60‐kg subject to 32.1 L/h for a 100‐kg subject). The model described the data adequately with high parameter precision and significant interindividual variability on the GH clearance and distribution volume. Additionally, high variability in the amount of secreted GH, driven by GHRH receptor activation, was identified (coefficient of variation = 90%).ConclusionThe stimulation of GH by GHRH was quantified and significant interindividual variability was identified on multiple parameters. This model sets the stage for further development of by inclusion of additional physiological components to quantify GH secretion in humans.

Ghrelin Does Not Directly Stimulate Secretion of Glucagon-like Peptide-1.

The gastrointestinal hormone ghrelin stimulates growth hormone secretion and appetite, but recent studies indicate that ghrelin also stimulates the secretion of the appetite-inhibiting and insulinotropic hormone glucagon-like peptide-1 (GLP-1). To investigate the putative effect of ghrelin on GLP-1 secretion in vivo and in vitro. A randomized placebo-controlled crossover study was performed in eight hypopituitary subjects. Ghrelin or saline was infused intravenously (1 pmol/min × kg) after collection of baseline sample (0 min), and blood was subsequently collected at time 30, 60, 90, and 120 minutes. Mouse small intestine was perfused (n = 6) and GLP-1 output from perfused mouse small intestine was investigated in response to vascular ghrelin administration in the presence and absence of a simultaneous luminal glucose stimulus. Ghrelin receptor expression was quantified in human (n = 11) and mouse L-cells (n = 3) by RNA sequencing and RT-qPCR, respectively. Ghrelin did not affect GLP-1 secretion in humans (area under the curve [AUC; 0-120 min]: ghrelin infusion = 1.37 ± 0.05 min × nmol vs. saline infusion = 1.40 ± 0.06 min × nmol [P = 0.63]), but induced peripheral insulin resistance. Likewise, ghrelin did not stimulate GLP-1 secretion from the perfused mouse small intestine model (mean outputs during baseline/ghrelin infusion = 19.3 ± 1.6/25.5 ± 2.0 fmol/min, n = 6, P = 0.16), whereas glucose-dependent insulinotropic polypeptide administration, used as a positive control, doubled GLP-1 secretion (P < 0.001). Intraluminal glucose increased GLP-1 secretion by 4-fold (P < 0.001), which was not potentiated by ghrelin. Finally, gene expression of the ghrelin receptor was undetectable in mouse L-cells and marginal in human L-cells. Ghrelin does not interact directly with the L-cell and does not directly affect GLP-1 secretion.

Sitagliptin Decreases Visceral Fat and Blood Glucose in Women With Polycystic Ovarian Syndrome.

Women with polycystic ovarian syndrome (PCOS) have decreased growth hormone (GH), which can result in increased visceral adiposity (VAT) and impaired vascular function. GH-releasing hormone, a dipeptidyl peptidase-4 (DPP4) substrate, stimulates GH secretion. We tested the hypothesis that DPP4 inhibition increases GH and improves glucose levels and vascular function in women with PCOS. Eighteen women with PCOS participated in a double-blind, crossover study. They received sitagliptin either 100 mg or placebo daily for 1 month, with crossover treatments separated by an 8-week washout. During each treatment, women underwent a 75-gram oral glucose tolerance test (OGTT) and assessments of vascular function and body composition. Overnight GH secretion was assessed via venous sampling every 10 minutes for 12 hours and analyzed using an automated deconvolution algorithm. During OGTT, sitagliptin increased glucagon-like peptide-1 (P < 0.001), early insulin secretion (from mean [± SD] insulinogenic index 1.9 ± 1.2 to 3.2 ± 3.1; P = 0.02), and decreased peak glucose (mean -17.2 mg/dL [95% CI, -27.7 to -6.6]; P < 0.01). At 1 month, sitagliptin decreased VAT (from 1141.9 ± 700.7 to 1055.1 ± 710.1 g; P = 0.02) but did not affect vascular function. Sitagliptin increased GH half-life (from 13.9 ± 3.6 to 17.0 ± 6.8 min, N = 16; P = 0.04) and interpulse interval (from 53.2 ± 20.0 to 77.3 ± 38.2 min, N = 16; P < 0.05) but did not increase mean overnight GH (P = 0.92 vs placebo). Sitagliptin decreased the maximal glucose response to OGTT and VAT. Sitagliptin did not increase overnight GH but increased GH half-life and the interpulse interval. This study was registered at www.clinicaltrials.gov as NCT02122380 prior to enrollment of the first participant.

Echinacoside Isolated from Cistanche tubulosa Putatively Stimulates Growth Hormone Secretion via Activation of the Ghrelin Receptor.

Cistanche species, the ginseng of the desert, has been recorded to possess many biological activities in traditional Chinese pharmacopoeia and has been used as an anti-aging medicine. Three phenylethanoid glycosides—echinacoside, tubuloside A, and acteoside—were detected in the water extract of Cistanche tubulosa (Schenk) R. Wight and the major constituent, echinacoside, was further purified. Echinacoside of a concentration higher than 10−6 M displayed significant activity to stimulate growth hormone secretion of rat pituitary cells. Similar to growth hormone-releasing hormone-6, a synthetic analog of ghrelin, the stimulation of growth hormone secretion by echinacoside was inhibited by [D-Arg1, D-Phe5, D-Trp7,9, Leu11]-substance P, an inverse agonist of the ghrelin receptor. Molecular modeling showed that all the three phenylethanoid glycosides adequately interacted with the binding pocket of the ghrelin receptor, and echinacoside displayed a slightly better interaction with the receptor than tubuloside A and acteoside. The results suggest that phenylethanoid glycosides, particularly echinacoside, are active constituents putatively responsible for the anti-aging effects of C. tubulosa and may be considered to develop as non-peptidyl analogues of ghrelin.

Melatonin’in Kanatlı Hayvanlarda Önemi

Intensive production practices, faulty maintenance and feeding, unsuitable keeping conditions, antinutritional factors in feeds and similar abnormalities lead to irregularities in both hormone and enzyme systems in poultry. Especially, due to disorders in endocrine system, a specific hormone, melatonin, can not be produced or underproduced, and thus its metabolic and physiological functions are negatively affected in the organisms. Melatonin (ML) is one of the important hormones that prevent metabolic and physiological disorders in poultry but does not attract attention by poultry scientist. ML regulates the brain's biological clock, acts on respiration, circulation, excretion, reproduction and immunity system. ML helps regulate feed consumption, energy metabolism and body heat. It also provides elimination of free radicals in the body. ML stimulates growth hormone secretion and, thus, effects growth performance of poultry positively. It is considered necesary to focus more effectively on the melatonin hormone, which is a positive contribution to animal welfare by correcting metabolic-physiological disorders in poultry. In this review, the definition of melatonin, its interaction with other hormones, its effect on the physiological and metabolic functions of poultry were examined.

Protective Effects of Ghrelin on Fasting-Induced Muscle Atrophy in Aging Mice.

Sarcopenia is the aging-associated progressive loss of skeletal muscle; however, the pathogenic mechanism of sarcopenia is not clear. The orexigenic hormone ghrelin stimulates growth hormone secretion, increases food intake, and promotes adiposity. Here we showed that fasting-induced muscle loss was exacerbated in old ghrelin-null (Ghrl-/-) mice, exhibiting decreased expression of myogenic regulator MyoD and increased expression of protein degradation marker MuRF1, as well as altered mitochondrial function. Moreover, acylated ghrelin and unacylated ghrelin treatments significantly increased mitochondrial respiration capacity in muscle C2C12 cells. Consistently, acylated ghrelin and unacylated ghrelin treatments effectively increased myogenic genes and decreased degradation genes in the muscle in fasted old Ghrl-/- mice, possibly by stimulating insulin and adenosine monophosphate-activated protein kinase pathways. Furthermore, Ghrl-/- mice showed a profile of pro-inflammatory gut microbiota, exhibiting reduced butyrate-producing bacteria Roseburia and ClostridiumXIVb. Collectively, our results showed that ghrelin has a major role in the maintenance of aging muscle via both muscle-intrinsic and -extrinsic mechanisms. Acylated ghrelin and unacylated ghrelin enhanced muscle anabolism and exerted protective effects for muscle atrophy. Because unacylated ghrelin is devoid of the obesogenic side effect seen with acylated ghrelin, it represents an attractive therapeutic option for sarcopenia.