ORCID Profile
0000-0003-1609-4358
Current Organisations
Garvan Institute of Medical Research
,
Western Sydney University
,
University of New South Wales
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Publisher: Bioscientifica
Date: 04-2022
DOI: 10.1530/EC-21-0375
Abstract: Androgen deprivation therapy (ADT), a principal therapy in patients with prostate cancer, is associated with the development of obesity, insulin resistance, and hyperinsulinemia. Recent evidence indicates that metformin may slow cancer progression and improves survival in prostate cancer patients, but the mechanism is not well understood. Circulating insulin-like growth factors (IGFs) are bound to high-affinity binding proteins, which not only modulate the bioavailability and signalling of IGFs but also have independent actions on cell growth and survival. The aim of this study was to investigate whether metformin modulates IGFs, IGF-binding proteins (IGFBPs), and the pregnancy-associated plasma protein A (PAPP-A) – stanniocalcin 2 (STC2) axis. In a blinded, randomised, cross-over design, 15 patients with prostate cancer on stable ADT received metformin and placebo treatment for 6 weeks each. Glucose metabolism along with circulating IGFs and IGFBPs was assessed. Metformin significantly reduced the homeostasis model assessment as an index of insulin resistance (HOMA IR) and hepatic insulin resistance. Metformin also reduced circulating IGF-2 ( P 0.05) and IGFBP-3 ( P 0.01) but increased IGF bioactivity ( P 0.05). At baseline, IGF-2 correlated significantly with the hepatic insulin resistance (r 2 = 0.28, P 0.05). PAPP-A remained unchanged but STC2 declined significantly ( P 0.05) following metformin administration. During metformin treatment, change in HOMA IR correlated with the change in STC2 (r 2 = 0.35, P 0.05). Metformin administration alters many components of the circulating IGF system, either directly or indirectly via improved insulin sensitivity. Reduction in IGF-2 and STC2 may provide a novel mechanism for a potential metformin-induced antineoplastic effect.
Publisher: Elsevier BV
Date: 03-2006
DOI: 10.1016/J.EJPHAR.2006.01.059
Abstract: To study acute tolerance, rats were anesthetized with interrupted i.v. allopregnanolone infusions where the "silent second" in the electroencephalogram (EEG) was the target. Animals were killed either directly at the first silent second or at the silent second level after 30 or 90 min of anaesthesia. Acute tolerance was demonstrated at 90 min of anaesthesia as earlier shown. In situ hybridization showed a decreased expression of the gamma-aminobutyric acid(A) (GABA(A)) receptor subunit alpha4mRNA amount in the thalamus ventral-posteriomedial nucleus of the tolerant rats. A parallel change in the abundance of the alpha4 subunit was detected with immunohistochemistry. The increase in maintenance dose rate (MDR) was significantly negatively correlated with the alpha4mRNA in the thalamus ventral-posteriomedial nucleus, and positively correlated with alpha2mRNA in different hippoc al subregions. There was also a positive relationship between the alpha1mRNA amounts in the different hippoc al subregions, with significant differences between groups. These changes in GABA(A) receptor subunits mRNA expression and protein (alpha4) might be of importance for the development of acute tolerance to allopregnanolone.
Publisher: Springer Netherlands
Date: 2008
Publisher: Springer Science and Business Media LLC
Date: 12-07-2008
DOI: 10.1007/S11154-008-9089-X
Abstract: Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Its actions are elaborated through the GH receptor (GHR). GHR signalling involves the role of at least three major pathways, STATs, MAPK, and PI3-kinase/Akt. GH receptor function can be modulated by changes to the ligand, to the receptor or by factors regulating signal transduction. Insights on the physico-chemical basis of the binding of GH to its receptor and the stoichiometry required for activation of the GH receptor-dimer has led to the development of novel GH agonists and antagonists. Owing to the fact that GH has short half-life, several approaches have been taken to create long-acting GHR agonists. This includes the pegylation, sustained release formulations, and ligand-receptor fusion proteins. Pegylation of a GH analogue (pegvisomant) which binds but not activate signal transduction forms the basis of a new successful approach to the treatment of acromegaly. GH receptors can be regulated at a number of levels, by modifying receptor expression, surface availability and signalling. Insulin, thyroid hormones and sex hormones are among hormones that modulate GHR through some of these mechanisms. Estrogens inhibit GH signalling by stimulating the expression of SOCS proteins which are negative regulators of cytokine receptor signalling. This review of GHR modulators will cover the effects of ligand modification, and of factors regulating receptor expression and signalling.
Publisher: Oxford University Press (OUP)
Date: 2015
DOI: 10.1530/EJE-14-0660
Abstract: To compare estimates by bioimpedance spectroscopy analysis (BIS) of extracellular water (ECW), fat mass (FM), and fat-free mass (FFM) against standard techniques of bromide dilution and dual energy X-ray absorptiometry (DXA) during intervention that causes significant changes in water compartments and body composition. Body composition analysis using BIS, bromide dilution, and DXA was performed in 71 healthy recreational athletes (43 men, 28 women aged 18–40 years BMI 24±0.4 kg/m 2 ) who participated in a double-blinded, randomized, placebo-controlled study of GH and testosterone treatment. The comparison of BIS with bromide dilution and DXA was analyzed using linear regression and the Bland–Altman method. At baseline, there was a significant correlation between BIS and bromide dilution-derived estimates for ECW, and DXA for FM and FFM ( P .001). ECW by BIS was 3.5±8.1% lower compared with bromide dilution, while FM was 22.4±26.8% lower and FFM 13.7±7.5% higher compared with DXA ( P .01). During treatment, the change in ECW was similar between BIS and bromide dilution, whereas BIS gave a significantly greater reduction in FM (19.4±44.8%) and a greater increase in FFM (5.6±3.0%) compared with DXA ( P .01). Significant differences in body composition estimates between the BIS and DXA were observed only in men, particularly during the treatment that caused greatest change in water compartments and body composition. In healthy adults, bioimpedance spectroscopy is an acceptable tool for measuring ECW however, BIS overestimates FFM and substantially underestimates FM compared with DXA.
Publisher: Oxford University Press (OUP)
Date: 03-2014
DOI: 10.1530/EJE-13-0835
Abstract: GH action is attenuated by estrogens and selective estrogen receptor modulators (SERMs) administered orally. During GH therapy in hypopituitary women, co-treatment with raloxifene, a SERM, induced a smaller gain in lean body mass (LBM) compared with estrogen, despite an equal reduction in IGF1. As a higher IGF-binding protein-3 (IGFBP3) level was observed with raloxifene co-treatment, we hypothesize that an increase in IGFBP3 reduced IGF1 bioactivity causing the attenuated anabolic effect. To assess the effects of 17β-estradiol (E 2 ) and raloxifene on bioactive IGF1. In study 1, 12 GH-deficient (GHD) women were randomized to raloxifene 120 mg/day or E 2 4 mg/day for 1 month. In study 2, 16 GHD women were randomized to 1 month GH treatment alone (0.5 mg/day) and in combination with raloxifene (60 mg/day) or E 2 (2 mg/day). We measured bioactive IGF1, immunoreactive IGF1 and IGF2, and IGFBP3 immunoreactivity and fragmentation. Raloxifene and estrogen suppressed ( P .05) total IGF1 equally in GHD and GH-replaced hypopituitary women. In GHD patients, neither raloxifene nor estrogen affected bioactive IGF1. GH significantly increased IGF1 bioactivity, an effect attenuated by co-treatment with raloxifene (Δ −23±7%, P .01) and estrogen (Δ −26±3%, P =0.06). Total IGF1 correlated ( r 2 =0.54, P .001) with bioactive IGF1, which represented 3.1±0.2% of the total IGF1, irrespective of the treatments. Total IGF2 was unchanged by raloxifene and estrogen treatment. IGFBP3 was significantly higher during raloxifene administration, whereas no differences in IGFBP3 fragmentation were observed. Raloxifene effect on bioactive IGF1 is similar to that of estrogen despite higher IGFBP3 levels during raloxifene administration. We conclude that the observed different effects on LBM between raloxifene and estrogen treatments cannot be explained by differences in IGF1 bioactivity.
Publisher: Massachusetts Medical Society
Date: 19-12-2013
DOI: 10.1056/NEJMC1313169
Publisher: Oxford University Press (OUP)
Date: 10-2015
DOI: 10.1530/EJE-15-0426
Abstract: Tamoxifen, a selective estrogen receptor modulator, suppresses GH secretion in women but not in men. It increases testosterone levels in men. As GH and testosterone stimulate fat metabolism, the metabolic consequences of tamoxifen may be greater in women than in men. To determine whether tamoxifen suppresses fat oxidation (Fox) to a greater degree in women than in men. An open-label study of ten healthy postmenopausal women and ten healthy men receiving 2-week treatment with tamoxifen (20 mg/day). GH response to arginine stimulation, serum levels of IGF1, testosterone and LH (men only), sex hormone binding globulin (SHBG) and whole body basal and postprandial Fox. In women, tamoxifen significantly reduced the mean GH response to arginine stimulation (Δ −87%, P .05) and circulating IGF1 levels (Δ −23.5±5.4%, P .01). Tamoxifen reduced postprandial Fox in women (Δ −34.6±10.3% P .05). In men, tamoxifen did not affect the GH response to arginine stimulation but significantly reduced mean IGF1 levels (Δ −24.8±6.1%, P .01). Tamoxifen increased mean testosterone levels (Δ 52±14.2% P .01). Fox was not significantly affected by tamoxifen in men. Tamoxifen attenuated the GH response to stimulation and reduced postprandial Fox in women but not in men. We conclude that at a therapeutic dose, the suppressive effect of tamoxifen on fat metabolism is gender-dependent. Higher testosterone levels may mitigate the suppression of GH secretion and Fox during tamoxifen treatment in men.
Publisher: The Endocrine Society
Date: 07-2011
DOI: 10.1210/JC.2010-2679
Abstract: Adipose tissue is a major target of GH action. GH stimulates lipolysis and reduces fat mass. The molecular mechanism underlying cellular and metabolic effects of GH in adipose tissue is not well understood. The aim of this study is to identify GH-responsive genes that regulate lipid metabolism in adipose tissue. Eight men with GH deficiency underwent measurement of plasma free fatty acid (FFA), whole-body lipid oxidation, and fat biopsies before and after 1 month of GH treatment (0.5 mg/d). Gene expression profiling was performed using Agilent 44K G4112F arrays using a two-color design. Differentially expressed genes were identified using an empirical Bayes, moderated t test, with a false discovery rate under 5%. Target genes were validated by quantitative RT-PCR. GH increased circulating IGF-I and FFA and stimulated fat oxidation. A total of 246 genes were differentially expressed, of which 135 were up-regulated and 111 down-regulated. GH enhanced adipose tissue expression of IGF-I and SOCS3. GH increased expression of patatin-like phospholipase domain containing 3 (PNPLA3), a novel triglyceride (TG) hydrolase, but not hormone-sensitive lipase (HSL), a classical TG hydrolase. GH repressed cell death-inducing DFFA-like effector A (CIDEA), a novel lipid droplets-associated protein, promoting TG storage. GH differentially regulated genes promoting diacylglycerol synthesis. GH suppressed hydroxysteroid (11β) dehydrogenase 1, which activates local cortisol production and genes encoding components of extracellular matrix and TGF-β signaling pathway. GH stimulates the TG/FFA cycle by regulating the expression of novel genes that enhance TG hydrolysis, reduce TG storage, and promote diacylglycerol synthesis. GH represses adipocyte growth, differentiation and inflammation.
Publisher: The Endocrine Society
Date: 12-2010
DOI: 10.1210/JC.2010-1477
Abstract: In men, the stimulation of GH and inhibition of LH secretion by testosterone requires aromatization to estradiol. Tamoxifen, a selective estrogen receptor modulator (SERM), possesses central estrogen antagonistic effect but peripheral hepatic agonist effect, lowering IGF-I. Thus, tamoxifen is likely to perturb the neuroendocrine regulation of GH and gonadal axes. Raloxifene, a SERM, is used for therapy of osteoporosis in both sexes. Its neuroendocrine effects in men are poorly understood. The aim was to compare the impact of raloxifene and tamoxifen on GH-IGF-I and gonadal axes in healthy men. We conducted a randomized, open-label crossover study. Ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d), with a 2-wk intervening washout period. We measured the GH response to arginine and circulating levels of IGF-I, LH, FSH, testosterone, and SHBG. Tamoxifen, but not raloxifene, significantly reduced IGF-I levels by 25±6% (P<0.01) and increased SHBG levels by 20±7% (P<0.05) at the higher therapeutic dose. There was a nonstatistically significant trend toward a reduction in the GH response to arginine with both SERMs. Both drugs significantly increased LH, FSH, and testosterone concentrations. The mean increase in testosterone (40 vs. 25% P<0.05) and LH (70 vs. 30% P<0.01) was significantly greater with tamoxifen than with raloxifene treatment. Tamoxifen, but not raloxifene, reduces IGF-I levels. Both SERMs stimulate the gonadal axis, with tamoxifen imparting a greater effect. We conclude that in therapeutic doses, raloxifene perturbs the GH and gonadal axes to a lesser degree than tamoxifen.
Publisher: The Endocrine Society
Date: 04-2011
DOI: 10.1210/JC.2010-2521
Abstract: GH and testosterone both exert protein-anabolic effects and may act synergistically. Liver and muscle are major sites of protein metabolism. Our objective was to determine whether the site of GH and testosterone interaction on protein metabolism is primarily hepatic or extrahepatic. In this open-label randomized crossover study, the impact on whole-body protein metabolism of oral (solely hepatic testosterone exposure) and transdermal (systemic testosterone exposure) testosterone replacement in the presence or absence of GH was compared. Eleven hypopituitary men with GH and testosterone deficiency were randomized to 2-wk treatments with transdermal testosterone (10 mg) or oral testosterone (40 mg), with or without GH replacement (0.6 mg/d). The dose of testosterone administered orally achieves physiological portal testosterone concentrations without spillover into the systemic circulation. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown, and leucine oxidation (Lox), a measure of irreversible protein loss, were estimated at the end of each treatment. In the absence of GH, neither transdermal nor oral testosterone affected LRa or Lox. GH therapy significantly increased LRa, an effect equally reduced by transdermal and oral testosterone administration. GH replacement alone did not significantly change Lox, whereas addition of testosterone treatment reduced Lox, with the effect not significantly different between transdermal and oral testosterone. In the doses used, testosterone stimulates protein anabolism by reducing protein breakdown and oxidation only in the presence of GH. Because the net effect on protein metabolism during GH therapy is not different between systemic and solely hepatic testosterone administration, we conclude that the liver is the primary site of this hormonal interaction.
Publisher: Wiley
Date: 09-2004
Publisher: Elsevier BV
Date: 10-2004
DOI: 10.1093/BJA/AEH233
Publisher: Wiley
Date: 12-2003
Abstract: That 3alpha-hydroxy-5alpha/beta-pregnane steroids (GABA steroids) have modulatory effects on the GABA-A receptor is well known. In behavioral studies in animals high exogenous dosages give concentrations not usually reached in the brain under physiological conditions. Animal and human studies show that GABA-A receptor-positive modulators like barbiturates, benzodiazepines, alcohol, and allopregnanolone have a bimodal effect. In pharmacological concentrations they are CNS depressants, anesthetic, antiepileptic, and anxiolytic. In low dosages and concentrations, reached endogenously, they can induce adverse emotional reactions in up to 20% of in iduals. GABA steroids can also induce tolerance to themselves and similar substances, and rebound occurs at withdrawal. Menstrual cycle-linked disorders can be understood by the concept that they are caused by the action of endogenously produced GABA-steroids through three mechanisms: (a) direct action, (b) tolerance induction, and (c) withdrawal effect. Ex les of symptoms and disorders caused by the direct action of GABA steroids are sedation, memory and learning disturbance, clumsiness, increased appetite, worsening of petit mal epilepsy, negative mood as tension, irritability and depression during hormone treatments, and the premenstrual dysphoric disorder (PMDD). A continuous exposure to GABA steroids causes tolerance, and women with PMDD are less sensitive to GABA-A modulators. A malfunctioning GABA-A receptor system is related to stress sensitivity, concentration difficulties, loss of impulse control, irritability, anxiety, and depression. An ex le of withdrawal effect is "catamenial epilepsy," when seizures increase during menstruation after the withdrawal of GABA steroids. Similar phenomena occur at stress since the adrenals produce GABA steroids during stress.
Publisher: The Endocrine Society
Date: 04-2012
DOI: 10.1210/JC.2011-3347
Abstract: In men, GH secretion is stimulated by estradiol derived locally from aromatization of testosterone. Recently, we showed that local estrogen also plays a major role in the central regulation of GH secretion in women. Tamoxifen and raloxifene are selective estrogen receptor modulators (SERMs), drugs that block central estrogen action but exert estrogen-like effects in the liver, inhibiting hepatic IGF-I production. The relative impact of SERMs on the GH-IGF-I axis in men and women has not been investigated. The aim of the study was to determine whether there is a gender difference in the impact of SERMs on the GH-IGF-I axis. We conducted a comparative, randomized, open-label, crossover study of tamoxifen and raloxifene. Ten healthy postmenopausal women and ten healthy men were randomized to 2-wk sequential treatment with tamoxifen (10 and 20 mg/d) and raloxifene (60 and 120 mg/d) with a washout of 2 wk between treatments. The GH response to arginine, IGF-I, testosterone, and SHBG was measured. In women, but not in men, tamoxifen significantly attenuated the GH response to arginine. The GH response was not significantly blunted by raloxifene in both sexes. Both SERMs significantly reduced mean IGF-I levels to a similar degree in men and women. In men, both SERMs significantly increased LH and testosterone levels. In summary, GH secretion was blunted by tamoxifen in women in the face of reduced IGF-I feedback inhibition but not in men in whom the gonadal axis was stimulated. We conclude that potential blunting of GH secretion in men by SERMs was counteracted by concomitant central stimulation of GH secretion by testosterone. In therapeutic doses, tamoxifen may induce detrimental metabolic effects in women, but not men.
Publisher: S. Karger AG
Date: 2001
DOI: 10.1159/000054679
Abstract: Female ovarian steroids influence mood and cognition, an effect presumably mediated by the serotonergic system. A key receptor in this interplay may be the 5-HT sub A /sub receptor subtype. We gave adult ovariectomized female rats subcutaneous pellets containing different dosages of 17β-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. 5-HT sub A /sub receptor mRNA levels were analyzed by in situ hybridization in the dorsal hippoc us, dorsal and median raphe nuclei, and entorhinal cortex. Estradiol treatment alone reduced 5-HT sub A /sub gene expression in the dentate gyrus and the CA2 region (17 and 19% decrease, respectively). Estradiol combined with progesterone supplementation increased 5-HT sub A /sub gene expression versus placebo in the CA1 and CA2 subregions of the dorsal hippoc us (16 and 30% increase, respectively). Concomitantly, 5-HT sub A /sub mRNA expression was decreased by 13% in the ventrolateral part of the dorsal raphe nuclei, while no changes were found in the median raphe nucleus and entorhinal cortex. Chronic effects of ovarian hormones on 5-HT sub A /sub receptor mRNA expression appear tissue-specific and involve hippoc al subregions and the raphe nuclei. Modulation of 5-HT sub A /sub receptor gene expression may be of importance for gonadal steroid effects on mood and cognition.
Publisher: Elsevier BV
Date: 02-2017
DOI: 10.1016/J.BEEM.2017.03.003
Abstract: Growth hormone (GH) regulates somatic growth, substrate metabolism and body composition. Sex hormones exert profound effect on the secretion and action of GH. Estrogens stimulate the secretion of GH, but inhibit the action of GH on the liver, an effect that occurs when administered orally. Estrogens suppress GH receptor signaling by stimulating the expression proteins that inhibit cytokine receptor signaling. This effect of estrogens is avoided when physiological doses of estrogens are administered via a non-oral route. Estrogen-like compounds, such as selective estrogen receptor modulators, possess dual properties of inhibiting the secretion as well as the action of GH. In contrast, androgens stimulate GH secretion, driving IGF-1 production. In the periphery, androgens enhance the action of GH. The differential effects of estrogens and androgens influence the dose of GH replacement in patients with hypopituitarism on concomitant treatment with sex steroids. Where possible, a non-oral route of estrogen replacement is recommended for optimizing cost-benefit of GH replacement in women with GH deficiency. Adequate androgen replacement in conjunction with GH replacement is required to achieve the full anabolic effect in men with hypopituitarism.
Publisher: Elsevier BV
Date: 05-2002
DOI: 10.1016/S0006-8993(02)02414-9
Abstract: The progesterone metabolite allopregnanolone (3alpha-OH-5alpha-pregnane-20-one) inhibits neural functions, enhancing the GABA induced GABA(A) receptor activation. This effect is benzodiazepine like and benzodiazepines are known to impair memory. Acute effects of allopregnanolone on the hippoc us dependent spatial learning in the Morris water maze have not been studied. Adult male Wistar rats where injected (i.v.) with allopregnanolone (2 mg/kg), or vehicle, daily for 11 days. At 8 or 20 min after each injection, studies of place navigation were performed in the Morris water maze. Allopregnanolone concentrations in plasma and in nine different brain areas where analyzed by radioimmunoassay. The latency to find the platform was increased 8 min after the allopregnanolone injection, while normal learning was seen after 20 min. Swim speed did not differ between groups. A higher number of rats were swimming close to the pool wall (thigmotaxis) in the 8 min allopregnanolone group compared to the other groups. Allopregnanolone concentrations in the brain tissue at 8 min were 1.5 to 2.5 times higher then at 20 min after the allopregnanolone injections. After vehicle injections the brain concentrations of allopregnanolone were at control levels. Plasma concentrations of allopregnanolone followed the same pattern as in the brain, with the exception of an increase 8 min after vehicle injections. The natural progesterone metabolite allopregnanolone can inhibit learning in the Morris water maze, an effect not caused by motor impairment. The learning impairment might be due to a combination of changed swimming behavior and difficulties in navigation.
Publisher: The Endocrine Society
Date: 28-03-2019
Abstract: Estrogen receptor antagonism by tamoxifen inhibits GH secretion in both men and postmenopausal women, suggesting that estrogen, albeit at low concentration, stimulates GH secretion. However, systemic estrogen replacement in postmenopausal women does not enhance GH secretion. To clarify the role of estrogen in mediating GH secretion, we investigated the effect of estrogen deprivation by using aromatase inhibitors. To determine whether estrogens mediate GH secretion in men and postmenopausal women. The effects of letrozole, an aromatase inhibitor, and tamoxifen were compared in an open-label crossover study. Eight men and 14 women received tamoxifen (20 mg/d) and letrozole (2.5 mg/d) for 2 weeks each. The primary endpoints were GH response to arginine stimulation and gonadal steroid levels. In men, letrozole significantly (P < 0.05) reduced the peak GH response to arginine (mean ± SEM Δ -49.4% ± 18.1%). Tamoxifen also reduced the mean peak GH, but this did not reach statistical significance. In postmenopausal women, letrozole did not affect peak GH, whereas tamoxifen significantly (P < 0.05) reduced peak GH (Δ -47.3% ± 10%). In men, letrozole reduced circulating estradiol (from 43.1 ± 2.8 to 12.7 ± 1.3 pmol/L P < 0.001), whereas in women estradiol was undetectable (<11 pmol/L) at baseline and throughout letrozole therapy. Because estrogen deprivation reduced circulating GH, we conclude that estrogens regulate GH secretion in men. In postmenopausal women, the neutral effect of aromatase inhibition is likely explained by pre-existing estrogen deficiency. The inhibition of GH secretion by tamoxifen in menopause suggests a non-estrogen receptor-mediated mechanism of action. In contrast to men, estrogen is unlikely to mediate GH secretion in postmenopausal women.
Publisher: Elsevier BV
Date: 2006
DOI: 10.1016/J.NEUROSCIENCE.2005.12.031
Abstract: The progesterone metabolite allopregnanolone, like benzodiazepines, reduces learning and impairs memory in rats. Both substances act as GABA agonists at the GABA-A receptor and impair the performance in the Morris water maze test. Women are during the menstrual cycle, pregnancy, and during hormone replacement therapy exposed to allopregnanolone or allopregnanolone-like substances for extended periods. Long-term benzodiazepine treatment can cause tolerance against benzodiazepine-induced learning impairments. In this study we evaluated whether a corresponding allopregnanolone tolerance develops in rats. Adult male Wistar rats were pretreated for 3 days with i.v. allopregnanolone injections (2 mg/kg) one or two times a day, or for 7 days with allopregnanolone injections 20 mg/kg intraperitoneally, twice a day. Thereafter the rats were tested in the Morris water maze for 5 days and compared with relevant controls. Rats pretreated with allopregnanolone twice a day had decreased escape latency, path length and thigmotaxis compared with the acute allopregnanolone group that was pretreated with vehicle. Pretreatment for 7 days resulted in learning of the platform position. However, the memory of the platform position was in these tolerant rats not as strong as in controls only given vehicle. Allopregnanolone treatment was therefore seen to induce a partial tolerance against acute allopregnanolone effects in the Morris water maze.
Publisher: Springer Science and Business Media LLC
Date: 30-08-2017
DOI: 10.1038/S41598-017-09968-7
Abstract: Human growth hormone (GH) is a naturally occurring hormone secreted by the pituitary gland with anabolic and growth-promoting activities. Since an increased availability of recombinant GH (rGH) for the treatment of GH-deficient patients, GH has been abused in sports and it is prohibited. “GH-isoform” and “biomarkers” tests are currently available for detection of GH abuse in sports, however both methods suffer from shortcomings. Here, we report on a proteomic approach to search for novel protein biomarkers associated with rGH administration in non-elite athletes. In this study, participants received either placebo or rGH for 8 weeks, and were followed over a 6-week washout period. We used 2-D DIGE and iTRAQ LC-MS/MS analyses to expose rGH-dependent marker proteins. Eight rGH-dependent plasma proteins namely apolipoproptein-L1, alpha-HS-glycoprotein, vitamin D-binding protein, afamin, insulin-like growth factor-binding protein-3, insulin-like growth factor-binding protein-ALS, lumican and extracellular matrix proteins 1 were identified. Apolipoprotein L1 and alpha-HS-glycoprotein were validated by Western blots to confirm their identities and expression patterns in rGH- and placebo-treated subject cohorts. Independent confirmation of these putative GH-responsive biomarkers would be of value for clinical practices and may have sports anti-doping utility.
Publisher: The Endocrine Society
Date: 03-2012
DOI: 10.1210/JC.2011-2837
Abstract: GH deficiency causes reduction in muscle and bone mass and an increase in fat mass (FM), the changes reversed by GH replacement. The beneficial effects of GH on fat oxidation and protein anabolism are attenuated more markedly by raloxifene, a selective estrogen receptor modulator, compared with 17β-estradiol. Whether this translates to a long-term detrimental effect on body composition is unknown. Our objective was to compare the effects of 17β-estradiol and raloxifene on FM, lean body mass (LBM), and bone mineral density (BMD) during GH replacement. This was an open-label randomized crossover study. Sixteen hypopituitary women received GH (0.5 mg/d) replacement for 24 months. One group received 17β-estradiol (2 mg/d) for the first 6 months before crossover to raloxifene (60 mg/d) for the remaining 18 months the other received the reversed sequence. Serum IGF-I and IGF-binding protein-3 concentrations, and FM, LBM, lumbar spine and femoral neck BMD were analyzed at baseline and at 6, 12, and 24 months within and between subjects. GH therapy significantly increased mean IGF-I during 17β-estradiol and raloxifene cotreatments equally, but elevated IGF-binding protein-3 to a greater extent during raloxifene cotreatment. GH cotreatment with 17β-estradiol increased LBM and lumbar spine and femoral neck BMD and reduced FM to a greater extent than with raloxifene. In hypopituitary women, raloxifene at therapeutic doses significantly attenuated the beneficial effects of GH on body composition compared with 17β-estradiol. Raloxifene has no metabolic advantage over 17β-estradiol during GH replacement.
Publisher: Oxford University Press (OUP)
Date: 04-2017
DOI: 10.1530/EJE-16-0868
Abstract: The urea cycle is a rate-limiting step for amino acid nitrogen elimination. The rate of urea synthesis is a true indicator of whole-body protein catabolism. Testosterone reduces protein and nitrogen loss. The effect of testosterone on hepatic urea synthesis in humans has not been studied. To determine whether testosterone reduces hepatic urea production. An open-label study. Eight hypogonadal men were studied at baseline, and after two weeks of transdermal testosterone replacement (Testogel, 100 mg/day). The rate of hepatic urea synthesis was measured by the urea turnover technique using stable isotope methodology, with 15 N 2 -urea as tracer. Whole-body leucine turnover was measured, from which leucine rate of appearance (LRa), an index of protein breakdown and leucine oxidation (Lox), a measure of irreversible protein loss, were calculated. Testosterone administration significantly reduced the rate of hepatic urea production (from 544.4 ± 71.8 to 431.7 ± 68.3 µmol/min P 0.01), which was paralleled by a significant reduction in serum urea concentration. Testosterone treatment significantly reduced net protein loss, as measured by percent Lox/LRa, by 19.3 ± 5.8% ( P 0.05). There was a positive association between Lox and hepatic urea production at baseline ( r 2 = 0.60, P 0.05) and after testosterone administration ( r 2 = 0.59, P 0.05). Testosterone replacement reduces protein loss and hepatic urea synthesis. We conclude that testosterone regulates whole-body protein metabolism by suppressing the urea cycle.
Publisher: Wiley
Date: 05-10-2009
DOI: 10.1111/J.1365-2265.2009.03524.X
Abstract: Fat mass is increased in hypogonadal men and the changes are reversed by testosterone replacement. Testosterone administration enhances whole body fat oxidation (Fox). Fat is oxidized in the liver and in extra-hepatic tissues. To determine whether the stimulation of Fox by testosterone arises primarily from the liver or from extra-hepatic tissues. This was an open-label cross-over study. Thirteen men with hypopituitarism (age 53.1 +/- 4.1 years) with both growth hormone (GH) and testosterone deficiency were studied sequentially after 2 weeks of treatment with transdermal testosterone (5 mg), no treatment, and stepwise incremental doses of oral crystalline testosterone (10, 20, 40 and 80 mg) in the absence of GH replacement. Serum testosterone, IGF-I, metabolic effects [resting energy expenditure (REE) and Fox], SHBG, and thyroid binding globulin (TBG) as markers of excessive hepatic androgen exposure, were measured at the end of each treatment period. When compared to the no-treatment phase, mean blood testosterone levels rose into the physiological range after transdermal testosterone delivery but did not significantly change after 10, 20, 40 or 80 mg oral testosterone treatment. Blood SHBG and TBG fell significantly with 80 mg oral testosterone dose but were unaffected by any other testosterone treatment. Fox increased significantly with transdermal but not with any dose of oral testosterone. Mean plasma IGF-I and REE were unaffected by testosterone, regardless of the route or dose. Short-term testosterone administration does not stimulate hepatic fat oxidation but enhances whole body fat oxidation by acting on extra-hepatic tissues.
Publisher: Oxford University Press (OUP)
Date: 09-2013
DOI: 10.1530/EJE-13-0406
Abstract: In hypopituitary men, oral delivery of unesterified testosterone in doses that result in a solely hepatic androgen effect enhances protein anabolism during GH treatment. In this study, we aimed to determine whether liver-targeted androgen supplementation induces protein anabolism in GH-replete normal women. Eight healthy postmenopausal women received 2-week treatment with oral testosterone at a dose of 40 mg/day (crystalline testosterone USP). This dose increases portal concentrations of testosterone, exerting androgenic effects on the liver without a spillover into the systemic circulation. The outcome measures were whole-body leucine turnover, from which leucine rate of appearance (LRa, an index of protein breakdown) and leucine oxidation (Lox, a measure of irreversible protein loss) were estimated, energy expenditure and substrate utilization. We measured the concentration of liver transaminases as well as of testosterone, SHBG and IGF1. Testosterone treatment significantly reduced LRa by 7.1±2.5% and Lox by 14.6±4.5% ( P .05). The concentration of liver transaminases did not change significantly, while that of serum SHBG fell within the normal range by 16.8±4.0% and that of IGF1 increased by 18.4±7.7% ( P .05). The concentration of peripheral testosterone increased from 0.4±0.1 to 1.1±0.2 nmol/l ( P .05), without exceeding the upper normal limit. There was no change in energy expenditure and fat and carbohydrate utilization. Hepatic exposure to unesterified testosterone by oral delivery stimulates protein anabolism by reducing protein breakdown and oxidation without inducing systemic androgen excess in women. We conclude that a small oral dose of unesterified testosterone holds promise as a simple novel treatment of protein catabolism and muscle wasting.
Publisher: Oxford University Press (OUP)
Date: 08-2017
DOI: 10.1530/EJE-17-0151
Abstract: Growth hormone (GH) stimulates hepatic synthesis of very-low-density lipoproteins (VLDL), whereas hepatic steatosis develops as a result of GH deficiency. Steatosis is also a complication of tamoxifen treatment, the cause of which is not known. As tamoxifen inhibits the secretion and action of GH, we hypothesize that it induces steatosis by inhibiting hepatic VLDL export. To investigate whether tamoxifen reduces hepatic VLDL secretion. Eight healthy, normolipidemic women (age: 64.4 ± 2.1 years) were studied in random sequence at baseline, after 2 weeks of tamoxifen (20 mg/day) and after 2 weeks of estradiol valerate (EV 2 mg/day) treatments, separated by a 4-week washout period. The kinetics of apolipoprotein B (apoB), the structural protein of VLDL particles, were measured using a stable isotope 2H 3 -leucine turnover technique. VLDL-apoB fractional catabolic rate (FCR) was determined using a multicompartment model. VLDL-apoB secretion was estimated as the product of FCR and VLDL-apoB concentration. GH response to arginine stimulation, circulating levels of IGF-1, FFA, and TG, along with TG content in VLDL were measured. Tamoxifen significantly ( P 0.05) reduced VLDL-apoB concentration and secretion by 27.3 ± 7.8% and 29.8 ± 10.2%, respectively. In contrast, EV did not significantly change VLDL-apoB concentration or secretion. Tamoxifen but not EV significantly reduced ( P 0.05) GH response to arginine stimulation. Both treatments significantly lowered ( P 0.05) circulating IGF-1. Inhibition of VLDL secretion may contribute to the development of fatty liver during tamoxifen therapy. As GH stimulates VLDL secretion, the development of steatosis may arise secondarily from GH insufficiency induced by tamoxifen.
Publisher: The Endocrine Society
Date: 08-2010
DOI: 10.1210/JC.2010-0476
Abstract: Paracrine regulation is emerging as a discrete control mechanism in the endocrine system. In hypogonadal men, stimulation of GH secretion by testosterone requires prior aromatization to estradiol, a paracrine effect unmasked by central estrogen receptor blockade with tamoxifen. In hypogonadal women, estrogen replacement via a physiological non-oral route fails to enhance GH secretion, indicating an absence of an endocrine effect. The aim was to investigate whether local estrogens produced from aromatization regulate GH secretion. We conducted an open-label, two-phase, crossover study. We compared the effects on GH secretion of tamoxifen with estradiol valerate in postmenopausal women. Ten women were treated with tamoxifen (10 and 20 mg/d) and estradiol valerate (2 mg/d) via oral route for 2 wk each, with a washout period of at least 6 wk. We measured the GH response to arginine and circulating levels of IGF-I and SHBG, markers of hepatic estrogen effect. The GH response to arginine was reduced by 10- and 20-mg tamoxifen in a dose-dependent manner and potentiated significantly (P<0.05) by estradiol valerate. Mean IGF-I concentration was reduced significantly with high-dose tamoxifen (P<0.01) and estradiol valerate treatment (P<0.05), whereas mean SHBG levels rose with both (P<0.01). Blunted GH response to stimulation occurring in the face of reduced IGF-I feedback inhibition with tamoxifen indicates that GH secretion was suppressed by estrogen receptor antagonism. Because circulating estradiol was unaffected, these data indicate a significant role of local estrogen in the central control of GH secretion. We conclude that aromatase mediates the paracrine control of GH secretion in women.
Publisher: Elsevier BV
Date: 02-2002
DOI: 10.1016/S0304-3940(01)02570-8
Abstract: Alterations in female gonadal hormones are associated with anxiety and mood changes. The aim of the present study was to determine influences of chronic gonadal hormone supplementation on 5-HT(2A) and 5-HT(2C) receptor mRNA levels in the ventral hippoc us and the frontal cerebral cortex. Ovariectomized adult female Sprague-Dawley rats (n=37) received implantation of subcutaneous pellets containing different dosages of 17beta-estradiol alone or in combination with progesterone, or placebo pellets, for 2 weeks. Serotonin receptor mRNA levels were analyzed by in situ hybridization in the ventral hippoc us and 5-HT(2A) receptor mRNA also in the frontal cortex. Estradiol treatment in combination with low-dose progesterone increased 5-HT(2A) receptor mRNA by 43% in the CA2 region of the ventral hippoc us, while estradiol combined with high-dose progesterone increased the expression of this gene by 84% in ventral CA1. 5-HT(2A) mRNA expression in the frontal cortex was not influenced by hormone manipulation. 5-HT(2C) receptor gene expression was in the ventral hippoc us decreased in the CA2, ventral CA1 and the subiculum subregions by high-dose estradiol treatment (8-20% decreases). Effects on mood by gonadal hormones can be mediated, at least partly, through influences on 5-HT(2A) and 5-HT(2C) receptor expression.
Publisher: The Endocrine Society
Date: 05-2010
DOI: 10.1210/JC.2009-2743
Abstract: The metabolic action of GH is attenuated by estrogens administered via the oral route. Selective estrogen receptor modulators lower IGF-I to a lesser degree than 17beta-estradiol in GH-deficient women, and their effect on fat and protein metabolism is unknown. The aim of the study was to compare the modulatory effects of 17beta-estradiol and raloxifene, a selective estrogen receptor modulator, on the metabolic action of GH. We conducted an open-label, two-group, randomized, two-period crossover study. Ten hypopituitary women received GH therapy alone (0.5 mg/d) and GH plus 17beta-estradiol (E(2) 2 mg/d). Eleven hypopituitary women received GH therapy alone and GH plus raloxifene (R 60 mg/d). The treatment duration was 1 month, with a 4-wk washout period. IGF-I, IGFBP-3, resting energy expenditure, and fat oxidation were quantified by indirect calorimetry. We measured whole body leucine turnover from which leucine rate of appearance and leucine incorporation into protein were estimated. GH significantly stimulated all outcome measures. During GH treatment, addition of R significantly reduced mean IGF-I but not IGFBP-3, whereas E(2) reduced both IGF-I and IGFBP-3 levels. Cotreatment with R but not E(2) significantly attenuated the stimulatory effects of GH on fat oxidation. There was a strong trend (P = 0.08) toward a greater reduction in leucine incorporation into protein after R compared to E(2) cotreatment. The modulatory effects of E(2) and R at therapeutic doses on GH action are different. R during GH therapy exerts a greater inhibitory effect on lipid oxidation and protein anabolism compared to E(2).
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 06-2018
Publisher: Springer Science and Business Media LLC
Date: 31-01-2012
Publisher: Elsevier BV
Date: 03-2010
DOI: 10.1016/J.ECL.2009.10.007
Abstract: Human growth hormone (GH) is widely abused by athletes however, there is little evidence that GH improves physical performance. Replacement of GH in GH deficiency improves some aspects of exercise capacity. There is evidence for a protein anabolic effect of GH in healthy adults and for increased lean body mass following GH, although fluid retention likely contributes to this increase. The evidence suggests that muscle strength, power, and aerobic exercise capacity are not enhanced by GH administration, however GH may improve anaerobic exercise capacity. There are risks of adverse effects of long-term abuse of GH. Sustained abuse of GH may lead to a state mimicking acromegaly, a condition with increased morbidity and mortality.
Publisher: Elsevier BV
Date: 08-2006
DOI: 10.1016/J.BRAINRESREV.2005.11.001
Abstract: This article will review neuroactive steroid effects on serotonin and GABA systems, along with the subsequent effects on cognitive functions. Neurosteroids (such as estrogen, progesterone, and allopregnanolone) are synthesized in the central and peripheral nervous system, in addition to other tissues. They are involved in the regulation of mood and memory, in premenstrual syndrome, and mood changes related to hormone replacement therapy, as well as postnatal and major depression, anxiety disorders, and Alzheimer's disease. Estrogen and progesterone have their respective hormone receptors, whereas allopregnanolone acts via the GABA(A) receptor. The action of estrogen and progesterone can be direct genomic, indirect genomic, or non-genomic, also influencing several neurotransmitter systems, such as the serotonin and GABA systems. Estrogen alone, or in combination with antidepressant drugs affecting the serotonin system, has been related to improved mood and well being. In contrast, progesterone can have negative effects on mood and memory. Estrogen alone, or in combination with progesterone, affects the brain serotonin system differently in different parts of the brain, which can at least partly explain the opposite effects on mood of those hormones. Many of the progesterone effects in the brain are mediated by its metabolite allopregnanolone. Allopregnanolone, by changing GABA(A) receptor expression or sensitivity, is involved in premenstrual mood changes and it also induces cognitive deficits, such as spatial-learning impairment. We have shown that the 3beta-hydroxypregnane steroid UC1011 can inhibit allopregnanolone-induced learning impairment and chloride uptake potentiation in vitro and in vivo. It would be important to find a substance that antagonizes allopregnanolone-induced adverse effects.
Publisher: Springer Science and Business Media LLC
Date: 2003
DOI: 10.2165/00023210-200317050-00003
Abstract: Premenstrual syndrome (PMS) is a menstrual cycle-linked condition with both mental and physical symptoms. Most women of fertile age experience cyclical changes but consider them normal and not requiring treatment. Up to 30% of women feel a need for treatment. The aetiology is still unclear, but sex steroids produced by the corpus luteum of the ovary are thought to be symptom provoking, as the cyclicity disappears in anovulatory cycles when a corpus luteum is not formed. Progestogens and progesterone together with estrogen are able to induce similar symptoms as seen in PMS. Symptom severity is sensitive to the dosage of estrogen. The response systems within the brain known to be involved in PMS symptoms are the serotonin and GABA systems. Progesterone metabolites, especially allopregnanolone, are neuroactive, acting via the GABA system in the brain. Allopregnanolone has similar effects as benzodiazepines, barbiturates and alcohol all these substances are known to induce adverse mood effects at low dosages in humans and animals. SSRIs and substances inhibiting ovulation, such as gonadotrophin-releasing hormone (GnRH) agonists, have proven to be effective treatments. To avoid adverse effects when high dosages of GnRH agonists are used, add-back hormone replacement therapy is recommended. Spironolactone also has a beneficial effect, although not as much as SSRIs and GnRH agonists.
Publisher: Elsevier BV
Date: 04-2015
DOI: 10.1016/J.METABOL.2014.12.005
Abstract: Formoterol is a β(2)-selective agonist that enhances protein anabolism in rodents. Whether formoterol imparts anabolic benefits in humans is unknown. The objective of the study was to investigate the effects of formoterol on whole body protein rates of turnover, oxidative loss and synthesis. Open label intervention study. Fifteen healthy adults (8 men). Volunteers were treated with oral formoterol 160 μg/day for one week. Changes in leucine turnover (LRa index of protein breakdown), oxidation (Lox irreversible protein loss) and incorporation into protein (LIP index of protein synthesis) were assessed using the whole body 1-[(13)C]leucine turnover technique before/after treatment. LRa, Lox and LIP correlated significantly with lean body mass (LBM). LRa, adjusted for LBM was significantly higher (P<0.05, 160±6 vs 109±3 μmol/min) in men but not fractional Lox and LIP (expressed as a proportion of LRa). Formoterol reduced LRa (-9±4%) in men but stimulated LRa (9±3%) in women. Formoterol significantly reduced (P<0.05) fractional Lox, an effect greater in women (-4±1 vs -1±1 %). It stimulated fractional LIP in women (∆4±1%, P<0.05) but not in men (∆1±1%). Formoterol induced an absolute anabolic effect that was greater in women (30 vs 8%). Heart rate, systolic and diastolic blood pressures were unaffected. In a therapeutic dose, formoterol stimulates protein anabolism in humans. It induced gender-dimorphic effects on protein turnover and on the partitioning of amino acids from oxidative loss toward protein synthesis, effects that are greater in women than in men. Formoterol holds promise as a treatment for sarcopenia.
Publisher: Oxford University Press (OUP)
Date: 02-2018
DOI: 10.1530/EJE-17-0844
Abstract: Growth hormone (GH) stimulates connective tissue and muscle growth, an effect that is potentiated by testosterone. Decorin, a myokine and a connective tissue protein, stimulates connective tissue accretion and muscle hypertrophy. Whether GH and testosterone regulate decorin in humans is not known. To determine whether decorin is stimulated by GH and testosterone. Randomized, placebo-controlled, double-blind study. 96 recreationally trained athletes (63 men, 33 women) received 8 weeks of treatment followed by a 6-week washout period. Men received placebo, GH (2 mg/day), testosterone (250 mg/week) or combination. Women received either placebo or GH (2 mg/day). Serum decorin concentration. GH treatment significantly increased mean serum decorin concentration by 12.7 ± 4.2% P 0.01. There was a gender difference in the decorin response to GH, with greater increase in men than in women (∆ 16.5 ± 5.3% P 0.05 compared to ∆ 9.4 ± 6.5% P = 0.16). Testosterone did not significantly change serum decorin. Combined GH and testosterone treatment increased mean decorin concentration by 19.5 ± 3.7% ( P 0.05), a change not significantly different from GH alone. GH significantly increases circulating decorin, an effect greater in men than in women. Decorin is not affected by testosterone. We conclude that GH positively regulates decorin in humans in a gender-dimorphic manner.
Publisher: Wiley
Date: 03-2015
DOI: 10.1111/IMJ.12629
Abstract: Doping in sport is a widespread problem not just among elite athletes, but even more so in recreational sports. In scientific literature, major emphasis is placed on doping detection, whereas detrimental effects of doping agents on athletes' health are seldom discussed. Androgenic anabolic steroids are well known for their positive effects on muscle mass and strength. Human growth hormone also increases muscle mass, although the majority of that is an increase in extracellular fluid and not the functional muscle mass. In recreational athletes, growth hormone does not have major effect on muscle strength, power or aerobic capacity, but stimulates anaerobic exercise capacity. Erythropoietin administration increases oxygen-carrying capacity of blood improving endurance measures, whereas systemic administration of beta-adrenergic agonists may have positive effect on sprint capacity, and beta-adrenergic antagonists reduce muscle tremor. Thus, there are certain drugs that can improve selective aspects of physical performance. However, most of the doping agents exert serious side-effects, especially when used in combination, at high doses and for a long duration. The extent of long-term health consequences is difficult to predict, but likely to be substantial, especially when gene doping is considered. This review summarises the main groups of doping agents used by athletes, with the main focus on their effects on athletic performance and adverse effects.
Publisher: American College of Physicians
Date: 04-05-2010
DOI: 10.7326/0003-4819-152-9-201005040-00007
Abstract: Growth hormone is widely abused by athletes, frequently with androgenic steroids. Its effects on performance are unclear. To determine the effect of growth hormone alone or with testosterone on body composition and measures of performance. Randomized, placebo-controlled, blinded study of 8 weeks of treatment followed by a 6-week washout period. Randomization was computer-generated with concealed allocation. (Australian-New Zealand Clinical Trials Registry registration number: ACTRN012605000508673) Clinical research facility in Sydney, Australia. 96 recreationally trained athletes (63 men and 33 women) with a mean age of 27.9 years (SD, 5.7). Men were randomly assigned to receive placebo, growth hormone (2 mg/d subcutaneously), testosterone (250 mg/wk intramuscularly), or combined treatments. Women were randomly assigned to receive either placebo or growth hormone (2 mg/d). Body composition variables (fat mass, lean body mass, extracellular water mass, and body cell mass) and physical performance variables (endurance [maximum oxygen consumption], strength [dead lift], power [jump height], and sprint capacity [Wingate value]). Body cell mass was correlated with all measures of performance at baseline. Growth hormone significantly reduced fat mass, increased lean body mass through an increase in extracellular water, and increased body cell mass in men when coadministered with testosterone. Growth hormone significantly increased sprint capacity, by 0.71 kJ (95% CI, 0.1 to 1.3 kJ relative increase, 3.9% [CI, 0.0% to 7.7%]) in men and women combined and by 1.7 kJ (CI, 0.5 to 3.0 kJ relative increase, 8.3% [CI, 3.0% to 13.6%]) when coadministered with testosterone to men other performance measures did not significantly change. The increase in sprint capacity was not maintained 6 weeks after discontinuation of the drug. Growth hormone dosage may have been lower than that used covertly by competitive athletes. The athletic significance of the observed improvements in sprint capacity is unclear, and the study was too small to draw conclusions about safety. Growth hormone supplementation influenced body composition and increased sprint capacity when administered alone and in combination with testosterone. The World Anti-Doping Agency.
Publisher: Elsevier BV
Date: 05-2011
DOI: 10.1016/J.TEM.2011.02.005
Abstract: There has been limited research and evidence that GH enhances physical performance in healthy adults or in trained athletes. Even so, human growth hormone (GH) is widely abused by athletes. In healthy adults, GH increases lean body mass, although it is possible that fluid retention contributes to this effect. The most recent data indicate that GH does not enhance muscle strength, power, or aerobic exercise capacity, but improves anaerobic exercise capacity. In fact, there are adverse effects of long-term GH excess such that sustained abuse of GH can lead to a state mimicking acromegaly, a condition with increased morbidity and mortality. This review will examine GH effects on body composition and physical performance in health and disease.
Start Date: 2014
End Date: 2017
Funder: National Health and Medical Research Council
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