Low-dose growth hormone treatment with diet restriction accelerates body fat loss, exerts anabolic effect and improves growth hormone secretory dysfunction in obese adults.

Growth hormone (GH) can induce an accelerated lipolysis. Impaired secretion of GH in obesity results in the consequent loss of the lipolytic effect of GH. Dietary restriction as a basic treatment for obesity is complicated by poor compliance, protein catabolism, and slow rates or weight loss. GH has an anabolic effect by increasing insulin-like growth factor (IGF)-I. We investigated the effects of GH treatment and dietary restriction on lipolytic and anabolic actions, as well as the consequent changes in insulin and GH secretion in obesity. 24 obese subjects (22 women and 2 men; 22-46 years old) were fed a diet of 25 kcal/kg ideal body weight (IBW) with 1.2 g protein/kg IBW daily and were treated with recombinant human GH (n = 12, 0.18 U/kg IBW/week) or placebo (n = 12, vehicle injection) in a 12-week randomized, double-blind and placebo-controlled trial. GH treatment caused a 1.6-fold increase in the fraction of body weight lost as fat and a greater loss of visceral fat area than placebo treatment (35.3 vs. 28.5%, p < 0.05). In the placebo group, there was a loss in lean body mass (-2.62 +/- 1.51 kg) and a negative nitrogen balance (-4.52 +/- 3.51 g/day). By contrast, the GH group increased in lean body mass (1.13 +/- 1.04 kg) and had a positive nitrogen balance (1.81 +/- 2.06 g/day). GH injections caused a 1.6-fold increase in IGF-I, despite caloric restriction. GH response to L-dopa stimulation was blunted in all subjects and it was increased after treatment in both groups. GH treatment did not induce a further increase in insulin levels during an oral glucose tolerance test (OGTT) but significantly decreased free fatty acid (FFA) levels during OGTT. The decrease in FFA area under the curve during OGTT was positively correlated with visceral fat loss. This study demonstrates that in obese subjects given a hypocaloric diet, GH accelerates body fat loss, exerts anabolic effects and improves GH secretion. These findings suggest a possible therapeutic role of low-dose GH with caloric restriction for obesity.     

Effects of growth hormone in patients with chronic renal failure: experience in children and adults

Recombinant human growth hormone (GH) has proven effective in promoting growth in short children with chronic renal failure before and after renal transplantation. The action of GH and its mediator insulin-like growth factor 1 on body composition, protein, glucose and bone metabolism offers additional therapeutic options. One might be the improvement of the catabolic state in adults with end-stage renal failure. In few pilot studies and two placebo-controlled studies of 6 months duration, GH treatment in adults on dialysis showed clear anabolic effects resulting in a significant increase in lean body mass.     

Effects of growth hormone on skeletal muscle

Human growth hormone (GH) is widely abused as a performance-enhancing anabolic drug by athletes and bodybuilders. However, the effects of GH on skeletal muscle mass, strength and fibre composition remain unclear. We therefore summarize in the following the current knowledge on the physiological role of GH in the regulation of skeletal muscle growth and function and evaluate its potential therapeutic potency as a muscle anabolic hormone. In states of GH deficiency, reduced muscle mass and strength are characteristic findings which can be reversed successfully by the supplementation of GH. In contrast, the currently available data suggest that GH administration alone or in combination with strength exercise has little, if any, effect on muscle volume, strength and fibre composition in non-GH-deficient healthy young individuals. This assumption is supported by the lack of evidence for a significant performance-enhancing effect of GH in athletes. However, further studies will be necessary to define patient populations which might benefit from GH treatment like frail elderly individuals in whom a GH-induced change into a more youthful muscle fibre composition has been reported.     

The impact of growth hormone on proteomic profiles: a review of mouse and adult human studies

Growth hormone (GH) is a protein that is known to stimulate postnatal growth, counter regulate insulin’s action and induce expression of insulin-like growth factor-1. GH exerts anabolic or catabolic effects depending upon on the targeted tissue. For instance, GH increases skeletal muscle and decreases adipose tissue mass. Our laboratory has spent the past two decades studying these effects, including the effects of GH excess and depletion, on the proteome of several mouse and human tissues. This review first discusses proteomic techniques that are commonly used for these types of studies. We then examine the proteomic differences found in mice with excess circulating GH (bGH mice) or mice with disruption of the GH receptor gene (GHR^?/?). We also describe the effects of increased and decreased GH action on the proteome of adult patients with either acromegaly, GH deficiency or patients after short-term GH treatment. Finally, we explain how these proteomic studies resulted in the discovery of potential biomarkers for GH action, particularly those related with the effects of GH on aging, glucose metabolism and body composition.     

Combination therapy with acipimox enhances the effect of growth hormone treatment on linear body growth in the normal and small-for-gestational-age rat

Growth hormone (GH) therapy is often associated with adverse side effects, including impaired insulin sensitivity. GH treatment of children with idiopathic short stature does not lead to an optimized final adult height. It has been demonstrated that FFA reduction induced by pharmacological antilipolysis can stimulate GH secretion per se in both normal subjects and those with GH deficiency. However, to date, no investigation has been undertaken to establish efficacy of combination treatment with GH and FFA regulators on linear body growth. Using a model of maternal undernutrition in the rat to induce growth-restricted offspring, we investigated the hypothesis that combination treatment with GH and FFA regulators can enhance linear body growth above that of GH alone. At postnatal day 28, male offspring of normally nourished mothers (controls) and offspring born with low birth weight [small for gestational age (SGA)] were treated with saline, GH, or GH (5 mg.kg(-1).day(-1)) in combination with acipimox (GH + acipimox, 20 mg.kg(-1).day(-1)) or fenofibrate (GH + fenofibrate, 30 mg.kg(-1).day(-1)) for 40 days. GH plus acipimox treatment significantly enhanced linear body growth in the control and SGA animals above that of GH, as quantified by tibial and total body length. Treatment with GH significantly increased fasting plasma insulin, insulin-to-glucose ratio, and plasma volumes in control and SGA animals but was not significantly different between saline and GH-plus-acipimox-treated animals. GH-induced lipolysis was blocked by GH plus acipimox treatment in both control and SGA animals, concomitant with a significant reduction in fasting plasma FFA and insulin concentrations. This is the first study to show that GH plus acipimox combination therapy, via pharmacological blocking of lipolysis during GH exposure, can significantly enhance the efficacy of GH in linear growth promotion and ameliorate unwanted metabolic side effects.     

Metformin restores responses to insulin but not to growth hormone in Sprague-Dawley rats

Administration of growth hormone (GH) increases muscle mass in F344 x BN rats, but not in Sprague-Dawley (S-D) rats. S-D rats are insulin-resistant and insulin responsiveness is required for the anabolic actions of GH. We hypothesized that correction of insulin resistance with metformin might also restore anabolic effects of GH. Treatment with GH (0.25 or 1.0 mg/kg twice daily for 9 days) had limited anabolic effects, reducing weight gain by 14%, increasing muscle glycogen content by 40% and increasing exercise capacity by 24%, but failing to increase muscle mass or to reduce fat mass. GH also impaired insulin responsiveness and increased visceral fat TNF content of visceral fat by 77%. Metformin enhanced insulin responsiveness in skeletal muscle, but failed to enhance anabolic effects of GH. Rats aged 14 weeks were treated for 21 days with metformin (320 mg/kg/day) and for the last 9 days, with GH (0.25 mg/kg, twice daily). Metformin caused a 2.3-fold increase in insulin-stimulated muscle glucose transport and a 20% reduction in muscle fatty acid oxidation, indicating increased glucose utilization. However, metformin did not augment GH-induced weight reduction. Metformin decreased visceral fat by 22% and subcutaneous fat by 20%, but no decreases were observed in the GH/metformin group. GH increased muscle glycogen by 40%, but the effect was reversed by metformin. VO(2max) was increased 24% by GH and 17% by metformin, but was not elevated in the GH/metformin group. GH increased TNF in visceral fat and the effect was augmented by metformin (144% increase). We conclude that metformin enhances some aspects of insulin responsiveness, but does not enhance anabolic responses to GH. The latter may, in part, be explained by the failure of metformin to prevent GH-induced elevation of TNF in visceral fat.     

Greater serum GH response to arm than to leg exercise performed at equivalent oxygen uptake

The aim of this study was to provide information concerning the mechanism of exercise-induced stimulation of growth hormone (GH) release in human subjects. For this reason serum GH as well as some hemodynamic variables and blood concentrations of noradrenaline (NA), insulin (IRI), lactate (LA), glucose (BG), and free fatty acids (FFA) were determined in seven healthy male subjects exercising on a bicycle ergometer with arms or legs and running on a treadmill at equivalent oxygen consumption levels. Significantly greater increases in serum GH concentration accompanied arm exercises than those observed during the leg exercises. This was accompanied by greater increases in heart rate, blood pressure, and plasma NA and blood lactate concentrations. Serum IRI decreased during both leg exercises and did not change during the arm exercise. There were no differences in BG and plasma FFA concentrations between the three types of exercise. The role of humoral and neural signals responsible for the greater GH response to arm exercise is discussed. The findings are consistent with the hypothesis that neural afferent signals sent by muscle "metabolic receptors" participate in the activation of GH release during physical exercise. It seems likely that the stimulation of these chemoreceptors is more pronounced when smaller muscle groups are engaged at a given work load. However, a contribution of efferent impulses derived from the brain motor centres to the control system of GH secretion during exercise is also possible.     

Growth hormone - hormone replacement for the somatopause?

Twenty-four-hour growth hormone (GH) secretion reaches a peak at around puberty and by the age of 21 has begun to decrease. Thereafter the fall in GH secretion is progressive such that by the age of 60 most adults have total 24-hour secretion rates indistinguishable from those of hypopituitary patients with organic lesions in the pituitary gland. Patterns of GH secretion are similar to those in younger people but GH pulses are markedly reduced in amplitude. Sleep and exercise remain the major stimuli for GH secretion. The fall in GH secretion seen with ageing coincides with changes in body composition and lipid metabolism that are similar to those seen in adults with GH deficiency. In elderly subjects, although GH secretion is markedly reduced, remaining GH secretion correlates closely with body composition (particularly with lean body mass and inversely with central abdominal fat). Pioneering studies carried out by Rudman showed that GH administration to elderly subjects with low insulin-like growth factor-I levels resulted in reversal of many of the changes associated with GH deficiency, namely an increase in lean body mass and bone mineral density and a reduction in body fat and plasma cholesterol. These changes were remarkably similar to those shown a year earlier in adults with GH deficiency given GH replacement. Subsequent studies of GH replacement in elderly adults have confirmed Rudman's initial observations but have been dominated by side effects which have led to a high number of dropouts. It is now clear that the elderly are very sensitive to GH and the doses used need to be very low, increased very slowly and tailored to the individual needs of each patient. Using this more cautious approach, recent studies have been very positive. A series of papers from Blackman's group, presented at the US endocrine meeting in San Diego in 1999, investigated the effects of GH with or without testosterone supplements (in men) and oestrogen supplements (in women). Their results showed positive effects of GH on lean body mass, central fat, low-density lipoprotein cholesterol and aerobic capacity. In many instances there was a positive interaction between GH and hormone replacement with testosterone and oestrogen, but it appeared that GH showed the most potent anabolic effects. Clearly more studies are needed before GH replacement for the elderly becomes established. Safety issues will require close scrutiny, but the data available so far are sufficiently positive to undertake large multicentre, placebo-controlled trials, particularly looking at endpoints associated with prevention of frailty and loss of independence.     

Acipimox enhances spontaneous growth hormone secretion in obese women

We hypothesized that a high circulating free fatty acid (FFA) concentration is involved in the pathogenesis of hyposomatotropism associated with obesity. To evaluate this hypothesis, 10 healthy premenopausal women (body mass index 33.8 +/- 1.0 kg/m(2)) were studied in the follicular phase of their menstrual cycle at two occasions with a time interval of at least 8 wk, where body weight remained stable. Subjects were randomly assigned to treatment with either acipimox (an inhibitor of lipolysis, 250 mg orally 4 times daily) or placebo in a double-blind crossover design, starting 1 day before admission until the end of the blood sampling period. Blood samples were taken during 24 h with a sampling interval of 10 min for assessment of growth hormone (GH) concentrations, and GH secretion was estimated by deconvolution analysis. Identical methodology was used to study GH secretion in a historical control group of age-matched normal weight women. GH secretion was clearly blunted in obese women (total daily release 66 +/- 10 vs. lean controls: 201 +/- 23 mU x l(Vd)(-1) x 24 h(-1), P = 0.005, where l(Vd) is lite of distribution volume). Acipimox considerably enhanced total (113 +/- 50 vs. 66 +/- 10 mU x l(Vd)(-1) x 24 h(-1), P = 0.02) and pulsatile GH secretion (109 +/- 49 vs. 62 +/- 30 mU x l(Vd)(-1) x 24 h(-1), P = 0.02), but GH output remained lower compared with lean controls. Further analysis did not show any relationship between the effects of acipimox on GH secretion and regional body fat distribution. In conclusion, acipimox unleashes spontaneous GH secretion in obese women. It specifically enhances GH secretory burst mass. This might mean that lowering of systemic FFA concentrations by acipimox modulates neuroendocrine mechanisms that orchestrate the activity of the somatotropic ensemble.     

How cancellous and cortical bones adapt to loading and growth hormone

There is great interest in the relationships between growth hormone (GH), muscle loading and bone, in part, because GH increases muscle mass which provides the largest signals that control bone modeling and remodeling. This study was designed to examine the effects of GH and muscle loading by exercise (EX) independently and in combination on bone and skeletal muscle. Thirteen-month-old female F344 rats were divided into 6 groups: Group 1, baseline controls (B); Group 2, agematched controls (C); Group 3, GH treated (2.5 mg rhGH/kg b. wt/day, 5 days per week); Group 4, voluntary wheel running exercise (EX); Group 5, GH+EX, and rats in Group 6 were food restricted (FR) to lower their body weight and examine the effects of decreased muscle load on bone. All animals, except the baseline controls, were sacrificed after 4.5 months. Growth hormone increased the body weight and tibial muscle mass of the rats markedly, while EX caused a slight decrease in body weight and partially inhibited the increase caused by GH in the GH+EX group. Food restriction greatly decreased body weight below that of age-matched controls but neither FR nor EX had a significant effect on the mass of the muscles around the tibia. Growth hormone and EX independently increased tibial diaphyseal cortical bone area (p<0.0001), cortical thickness (p<0.0001), cortical bone mineral content (p<0.0001), periosteal perimeter (p<0.0001) and bone strength-strain index (SSI) (p<0.0001). The effects of GH were more marked, and the combination of GH and EX produced additive effects on many of the tibial diaphyseal parameters including bone SSI. GH+EX, but not GH or EX alone caused a significant increase in endocortical perimeter (p<0.0001). In the FR rats, cortical bone area and cortical mineral content increased above the baseline level (p<0.0001) but were below the levels for age-matched controls (p<0.0001). In addition, marrow area, endocortical perimeter and endocortical bone formation rate increased significantly in the FR rats (p<0.01, p<0.0001, p<0.0001). Three-point bending test of right tibial diaphysis resulted in maximum force (Fmax) values that reflected the group differences in indices of tibial diaphyseal bone mass except that GH+EX did not produce additive effect on Fmax. The latter showed good correlation with left tibial diaphyseal SSI (r=0.857, p<0.0001) and both indices of bone strength correlated well with tibial muscle mass (r=0.771, Fmax; r=0.700, SSI; p<0.0001). We conclude that the bone anabolic effects of GH with or without EX may relate, in part, to increased load on bone from tibial muscles and body weight, which were increased by the hormone. The osteogenic effects of EX with or without GH may relate, in part, to increased frequency of muscle load on bone as EX decreased body weight (p<0.05) but had no significant effect on tibial muscle mass. The enhanced loss of endocortical bone by FR may relate, in part, to decreased load on bone due to low body weight (p<0.0001) as FR did not cause a significant decrease in tibial muscle mass (p=0.357). The roles of humoral and local factors in the bone changes observed remain to be established.     

Bone densitometry: assessing the effects of growth hormone treatment in adults

Dual-energy X-ray absorptiometry (DXA) is the reference method for the measurement of bone mineral mass at different skeletal sites. It has been widely used in recent years to assess the effects of growth hormone (GH) treatment on bone metabolism. In normal individuals, bone mineral content (BMC) and density (BMD), as assessed using DXA, correlate with body size. Therefore, using DXA in patients with congenital GH deficiency (GHD), who have a smaller body frame, would be expected to result in lower bone mass. Thus, comparisons with reference data derived from populations of normal body size are invalid. The evaluation of the effects of GH administration should take into account the possible effects of GH on bone size, not only in children, but also in adults. The enlargement of bone, due to stimulation of the periosteal apposition, may partially mask an increase in BMC, resulting in little or no change in BMD. The ability of GH to affect bone area therefore requires analysis of the possible changes in bone area and BMC, as well as BMD. This issue has been poorly handled in the studies published to date. Lastly, the acceleration of bone turnover induced by GH leads to an increase in bone remodelling space, which in turn is associated with a reduction in BMC and BMD, independent of the net balance between breakdown and formation in each metabolic unit. This bone loss is completely reversible when the remodelling space returns to previous levels. This phenomenon must be taken into account when analysing the effects of GH treatment on bone mass, because a net gain in bone mass may be found in long-term GH treatment or after GH discontinuation, even if bone loss was evident during the first 6 months of treatment. In conclusion, the interpretation of bone density data in patients with GHD, and after GH administration, should take into account some of the methodological aspects of bone densitometry, as well as the specific actions of GH on bone metabolism and body composition.     

Acute exposure to GH during exercise stimulates the turnover of free fatty acids in GH-deficient men.

The secretion of growth hormone (GH) increases acutely during exercise, but whether this is associated with the concomitant alterations in substrate metabolism has not previously been studied. We examined the effects of acute GH administration on palmitate, glucose, and protein metabolism before, during, and after 45 min of moderate-intensity aerobic exercise in eight GH-deficient men (mean age = 40.8 +/- 2.9 yr) on two occasions, with (+GH; 0.4 IU GH) and without GH administered (-GH). A group of healthy controls (n = 8, mean age = 40.4 +/- 4.2 yr) were studied without GH. The GH replacement during exercise on the +GH study mimicked the endogenous GH profile seen in healthy controls. No significant difference in resting free fatty acid (FFA) flux was found between study days, but during exercise a greater FFA flux was found when GH was administered (211 +/- 26 vs. 168 +/- 28 micromol/min, P < 0.05) and remained elevated throughout recovery (P < 0.05). With GH administered, the exercise FFA flux was not significantly different from that observed in control subjects (188 +/- 14 micromol/min), but the recovery flux was greater on the +GH day than in the controls (169 +/- 17 vs. 119 +/- 11 micromol/min, respectively, P < 0.01). A significant time effect (P < 0.01) for glucose rate of appearance from rest to exercise and recovery occurred in the GH-deficient adults and the controls, whereas there were no differences in glucose rate of disappearance. No significant effect across time was found for protein muscle balance. In conclusion, 1) acute exposure to GH during exercise stimulates the FFA release and turnover in GH-deficient adults, 2) GH does not significantly impact glucose or protein metabolism during exercise, and 3) the exercise-induced secretion of GH plays a significant role in the regulation of fatty acid metabolism.     

Growth hormone and testosterone interact positively to enhance protein and energy metabolism in hypopituitary men

We investigated the impact of growth hormone (GH) alone, testosterone (T) alone, and combined GH and T on whole body protein metabolism. Twelve hypopituitary men participated in two studies. Study 1 compared the effects of GH alone with GH plus T, and study 2 compared the effects of T alone with GH plus T. IGF-I, resting energy expenditure (REE), and fat oxidation (F(ox)) and rates of whole body leucine appearance (R(a)), oxidation (L(ox)), and nonoxidative leucine disposal (NOLD) were measured. In study 1, GH treatment increased mean plasma IGF-I (P < 0.001). GH did not change leucine R(a) but reduced L(ox) (P < 0.02) and increased NOLD (P < 0.02). Addition of T resulted in an additional increase in IGF-I (P < 0.05), reduction in Lox (P < 0.002), and increase in NOLD (P < 0.002). In study 2, T alone did not alter IGF-I levels. T alone did not change leucine R(a) but reduced L(ox) (P < 0.01) and increased NOLD (P < 0.01). Addition of GH further reduced L(ox) (P < 0.05) and increased NOLD (P < 0.05). In both studies, combined treatments on REE and F(ox) were greater than either alone. In summary, GH-induced increase of circulating IGF-I is augmented by T, which does not increase IGF-I in the absence of GH. T and GH exerted independent and additive effects on protein metabolism, F(ox) and REE. The anabolic effects of T are independent of circulating IGF-I.     

American Association of Clinical Endocrinologists and American College of Endocrinology Disease State Clinical Review: Update on Growth Hormone Stimulation Testing and Proposed Revised Cut-Point for the Glucagon Stimulation Test in the Diagnosis Of Adult Growth Hormone Deficiency

Objective: The clinical features of adult GH deficiency (GHD) are nonspecific, and GH stimulation testing is often required to confirm the diagnosis. However, diagnosing adult GHD can be challenging due to the episodic and pulsatile GH secretion, concurrently modified by age, gender, and body mass index (BMI).Methods: PubMed searches were conducted to identify published data since 2009 on GH stimulation tests used to diagnose adult GHD. Relevant articles in English language were identified and considered for inclusion in the present document.Results: Testing for confirmation of adult GHD should only be considered if there is a high pretest probability, and the intent to treat if the diagnosis is confirmed. The insulin tolerance test (ITT) and glucagon stimulation test (GST) are the two main tests used in the United States. While the ITT has been accepted as the gold-standard test, its safety concerns hamper wider use. Previously, the GH–releasing hormone-arginine test, and more recently the GST, are accepted alternatives to the ITT. However, several recent studies have questioned the diagnostic accuracy of the GST when the GH cut-point of 3 μg/L is used and have suggested that a lower GH cut-point of 1 μg/L improved the sensitivity and specificity of this test in overweight/obese patients and in those with glucose intolerance.Conclusion: Until a potent, safe, and reliable test becomes available, the GST should remain as the alternative to the ITT in the United States. In order to reduce over-diagnosing adult GHD in overweight/obese patients with the GST, we propose utilizing a lower GH cut-point of 1 μg/L in these subjects. However, this lower GH cut-point still needs further evaluation for diagnostic accuracy in larger patient populations with varying BMIs and degrees of glucose tolerance.Abbreviations:AACE = American Association of Clinical EndocrinologistsBMI = body mass indexGH = growth hormoneGHD = GH deficiencyGHRH = GH–releasing hormoneGHS = GH secretagogueGST = glucagon stimulation testIGF = insulin-like growth factorIGFBP-3 = IGF-binding protein 3ITT = insulin tolerance testROC = receiver operating characteristicWB-GST = weight-based GST     

Metabolic regulation of growth hormone by free fatty acids, somatostatin, and ghrelin in HIV-lipodystrophy

Human immunodeficiency virus (HIV)-lipodystrophy is a syndrome characterized by changes in fat distribution and insulin resistance. Prior studies suggest markedly reduced growth hormone (GH) levels in association with excess visceral adiposity among patients with HIV-lipodystrophy. We investigated mechanisms of altered GH secretion in a population of 13 male HIV-infected patients with evidence of fat redistribution, compared with 10 HIV-nonlipodystrophic patients and 11 male healthy controls similar in age and body mass index (BMI). Although similar in BMI, the lipodystrophic group was characterized by increased visceral adiposity, free fatty acids (FFA), and insulin and reduced extremity fat. We investigated ghrelin and the effects of acute lowering of FFA by acipimox on GH responses to growth hormone-releasing hormone (GHRH). We also investigated somatostatin tone, comparing GH response to combined GHRH and arginine vs. GHRH alone with a subtraction algorithm. Our data demonstrate an equivalent number of GH pulses (4.1 +/- 0.6, 4.7 +/- 0.8, and 4.5 +/- 0.3 pulses/12 h in the HIV-lipodystrophic, HIV-nonlipodystrophic, and healthy control groups, respectively, P > 0.05) but markedly reduced GH secretion pulse area (1.14 +/- 0.27 vs. 4.67 +/- 1.24 ng.ml(-1).min, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 1.14 +/- 0.27 vs. 3.18 +/- 0.92 ng.ml(-1).min, P < 0.05 HIV-lipodystrophic vs. control), GH pulse area, and GH pulse width in the HIV-lipodystrophy patients compared with the control groups. Reduced ghrelin (418 +/- 46 vs. 514 +/- 37 pg/ml, P < 0.05, HIV-lipodystrophic vs. HIV-nonlipodystrophic; 418 +/- 46 vs. 546 +/- 45 pg/ml, P < 0.05, HIV-lipodystrophic vs. control), impaired GH response to GHRH by excess FFA, and increased somatostatin tone contribute to reduced GH secretion in patients with HIV-lipodystrophy. These data provide novel insight into the metabolic regulation of GH secretion in subjects with HIV-lipodystrophy.     

Overwinter fasting and re-feeding in rainbow trout: plasma growth hormone and cortisol levels in relation to energy mobilisation

This study investigated the roles of cortisol and growth hormone (GH) during a period of fasting in overwintering salmonid fish. Indices of carbohydrate (plasma glucose, liver glycogen), lipid (plasma free fatty acids (FFAs)) and protein metabolism (plasma protein, total plasma amino acids) were determined, together with plasma GH, cortisol and somatolactin (SL) levels at intervals in three groups of rainbow trout (continuously fed; fasted for 9 weeks then fed; fasted for 17 weeks). In fasted fish, a decline in body weight and condition factor was accompanied by reduced plasma glucose and hepatic glycogen and increased plasma FFA. No consistent elevation of plasma GH occurred until after 8 weeks of fasting when plasma GH levels increased ninefold. No changes were observed in plasma total protein and AA until between weeks 13 and 17 when both were reduced significantly. When previously fasted fish resumed feeding, plasma glucose and FFA, and hepatic glycogen levels rapidly returned to control values and weight gain resumed. No significant changes in plasma cortisol levels, related to feeding regime, were evident at any point during the study and there was no evidence that SL played an active role in the response to fasting. The results suggest that overwinter fasting may not represent a significant nutritional stressor to rainbow trout and that energy mobilisation during fasting may be achieved without the involvement of GH, cortisol or SL.