The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance.

Beshyah, Salem A.; Henderson, AD; Niththyananthan, R.; Skinner, E. R.; Anyaoku, V.; Richmond, W.; Sharp, Patrick; Johnston, Desmond G.

doi:10.1210/jcem.80.2.7852490

Cited by 90 publications

(82 citation statements)

References 38 publications

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“…Prospective dose response studies will be necessary to decide this. Our ®nding that HDL cholesterol was unchanged after GH treatment is in accordance with some, 11,17±19,28 but not with other, 15,16,26,29,30 studies in which increased levels were found. The reason for this discrepancy is not readily explained.…”

Section: Discussionsupporting

confidence: 90%

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study

et al. 1998

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OBJECTIVE: To investigate whether the changes in lipoproteins following growth hormone (GH) substitution in GH de®cient (GHD) adults are determined by the concomitant changes in body composition and physical ®tness in a controlled long-term study. DESIGN: A randomized, double-blind, placebo-controlled trial with GH (2 IU/m 2 ) or placebo given for 12 months. SUBJECTS: Twenty-seven patients (18 male, 9 female, aged 21±61 y) with adult onset GH de®ciency. Comparisons were made with age-and gender-matched healthy adults. MEASUREMENTS: Serum triglycerides (TG) and lipoproteins, body composition (Dual-Energy X-ray Absorptiometry and computerized tomography), and exercise capacity (V Á O 2 -max measured by bicycle ergometry) were measured at baseline and after 12 months. RESULTS: Baseline values of total cholesterol, low-density lipoprotein (LDL) and serum triglycerides were signi®cantly higher in GHD adults compared to normal subjects (P`0.001, P`0.001, P 0.004, respectively) whereas no difference in high-density lipoprotein (HDL) or lipoprotein (a) (Lp(a)) was found. After one year of GH treatment total cholesterol decreased signi®cantly (P 0.02). Serum LDL decreased after GH and increased after placebo, but the difference in delta values was not signi®cant (P 0.12). Serum HDL and TG concentrations were unchanged. Lp(a) increased but not signi®cantly. Serum total and LDL cholesterol remained signi®cantly elevated after one year of GH treatment. Signi®cant reductions in total and visceral adiposity, and improved exercise capacity were also recorded after GH treatment. In normal subjects, serum total cholesterol and TG correlated positively with age, subcutaneous fat and intraabdominal fat, and negatively with V Á O 2 -max. Serum LDL correlated positively with age. In GHD patients, baseline values of serum TG correlated positively with subcutaneous fat and serum insulin. During treatment, no signi®cant correlations were found between the changes in lipoproteins and in body composition. CONCLUSION: The cholesterol lowering effect of GH is not determined by the concomitant decrease in adiposity, which supports the concept of a direct effect of GH on lipoprotein metabolism.

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Section: Discussionsupporting

confidence: 90%

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study

et al. 1998

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“…high triglycerides, low HDL cholesterol, elevated small dense LDL) may be common (14-50%), but complete ALP is relatively uncommon (14% in GHD and 7% after GHRT). Therefore, it remains to be established whether quantitative and qualitative changes of lipids are the main cause for the increased cardiovascular mortality and morbidity found in hypopituitary patients with GHD (39,40). Similarly, the lack of effect of GHRT on LDL size in the present study does not support the concept that a possible effect of GHRT on cardiovascular mortality, as recently suggested (41), is related to the effect of GH on lipid metabolism.…”

Section: Ghd Versus Controls (Pz)contrasting

confidence: 85%

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

Rizzo

Trepp²,

Berneis³

et al. 2007

eur j endocrinol

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Objective: Patients with growth hormone deficiency (GHD) have increased cardiovascular risk and may show elevated triglyceride and reduced high density lipoprotein (HDL) cholesterol concentrations, two lipid abnormalities usually accompanied by increased small dense LDL in the 'atherogenic lipoprotein phenotype' (ALP). In the present study, we directly investigated (1) whether hypopituitary patients with GHD have increased small dense LDL; (2) whether growth hormone replacement therapy (GHRT) beneficially impact on such particles; (3) the prevalence of ALP in GHD and GHRT patients. Design and methods: In 14 hypopituitary patients with GHD (44G13 years, body mass index (BMI) 27G3) before and after 4 months of GHRT, and in 11 healthy age-and BMI-matched controls we measured plasma lipids and LDL size and subclasses by gradient gel electrophoresis. Results: Compared with controls, GHD showed increased triglycerides (PZ0.0024), similar total and LDL cholesterol levels and a tendency towards reduced HDL cholesterol concentrations (PZ0.0894). GHRT reduced total and LDL cholesterol levels (PZ0.0303 and 0.0120 respectively), but no effect was found on triglycerides and HDL cholesterol levels. LDL size was unchanged in GHD versus controls (269G9 vs 274G6 Å , PZns), but LDL subclass analysis revealed a shift towards more dense particles (PZ0.0046). GHRT had no significant impact on LDL size and subclasses. The prevalence of ALP was 14% in GHD and 7% in GHRT. Conclusions: In GHD patients, individual features of ALP (including increased small dense LDL) may be common, but complete ALP is relatively uncommon. Short-term replacement therapy seems to be ineffective on such lipid alterations, but the effect of a longer GHRT remains to be assessed.

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“…In this study, we have not evaluated the plasma levels of low density lipoprotein (LDL)/high density lipoprotein (HDL) cholesterol, but our finding of decreased cholesterol levels in hexarelin-treated obese rats could be due to a decrease in LDL cholesterol with minor changes in HDL cholesterol. In fact, it has been shown in humans that both the GHRP-induced GH release and activation of the HPA axis cause changes in lipoprotein metabolism, decreasing LDL cholesterol and increasing HDL cholesterol (Berg & Nilsson-Ehle 1994, Beshyah et al 1995. Furthermore, changes in the levels of each plasma lipoprotein and, obviously, of total cholesterol seem dependent on the length of GHRP treatment.…”

Section: Discussionmentioning

confidence: 99%

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

Gennaro-Colonna

Rossoni²,

Cocchi³

et al. 2000

Journal of Endocrinology

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Genetically obese male Zucker rats have an impaired secretion of GH, coupled to hyperinsulinemia, hyperlipidemia and glucose intolerance. The aim of this study was to evaluate whether a chronic treatment with hexarelin, a synthetic enkephalin-derived hexapeptide with a potent GH-releasing activity, might be able to ameliorate the somatotropic function and reverse some metabolic alterations associated with obesity in male obese Zucker rats. Furthermore, as decreased GH secretion and insulin resistance are associated with increased cardiovascular risk, we also tested the capacity of hexarelin to prevent postischemic ventricular dysfunction in hearts of male obese Zucker rats. Obese and lean male rats of the Zucker strain were treated with hexarelin (80 µg/kg, b.i.d., s.c.) or saline (1 ml/kg, b.i.d., s.c.) for 30 days. An acute hexarelin injection (80 µg, s.c.) at the 28th day of treatment elicited a rise in plasma GH levels in lean but not in obese rats (pretreated or not with hexarelin); lean rats chronically treated with hexarelin showed a greater increase in plasma GH as compared with control counterparts. At the end of the experiment, pituitary GH mRNA levels were significantly reduced in obese rats and hexarelin administration failed to increase pituitary GH mRNA and IGF-I concentrations in plasma and heart. Chronic treatment with hexarelin increased insulinemia and blood glucose levels in obese but not in lean rats, left unaltered the high triglyceride levels but significantly decreased plasma cholesterol concentrations in obese rats. Heart preparations from lean and obese Zucker rats treated with saline, subjected to low flow ischemia and reperfusion, showed at reperfusion: a) a low recovery of postischemic left ventricular developed pressure (LVDP), coupled to a substantial increase in coronary perfusion pressure, and b) a marked increase in creatine kinase released in the perfusates. Hexarelin administration for 30 days counteracted the heart ischemic damage both in lean and obese Zucker rats. In fact, the recovery of LVDP at reperfusion was significantly higher than in controls and the increase in coronary resistance was minimal. Collectively, these data indicate that a 30-day treatment with hexarelin was unable to improve somatotropic function in male obese Zucker rats but was successful in decreasing plasma cholesterol concentrations. Hexarelin exerted a cardioprotective effect in both lean and obese rats. The heart-protective activity afforded by the peptide was divorced from any stimulation of the GH axis and is probably exerted through activation of specific cardiac receptors.

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The effects of short and long-term growth hormone replacement therapy in hypopituitary adults on lipid metabolism and carbohydrate tolerance.

Cited by 90 publications

References 38 publications

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study

The favourable effects of growth hormone (GH) substitution on hypercholesterolaemia in GH-deficient adults are not associated with concomitant reductions in adiposity. A 12 month placebo-controlled study

Atherogenic lipoprotein phenotype and low-density lipoprotein size and subclasses in patients with growth hormone deficiency before and after short-term replacement therapy

Endocrine, metabolic and cardioprotective effects of hexarelin in obese Zucker rats

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