The secretory pattern of GH in the mature rat is sexually differentiated. In male rats GH is secreted in pulses occurring at regular 3- to 4-h intervals. In females the pulses are lower and plasma GH levels between the pulses are higher than in males. The continuous presence of testosterone appears to be necessary to maintain low basal GH levels in adult male rats. Neonatal, but not prepubertal, gonadectomy decreases GH pulse height in adult male rats to female levels. Administration of testosterone neonatally to castrated animals returns GH pulse height to normal suggesting that neonatal testicular androgen secretion is one determinant for GH pulse height in adult male rats. Administration of testosterone neonatally or during adult life to neonatally ovariectomized rats also produces higher GH pulses. In contrast to testosterone, estrogens elevate basal plasma GH levels and suppress the GH pulses under some conditions. Estrogens may stimulate basal GH secretion by acting directly on the pituitary. The physiological significance of the secretory pattern of GH has been investigated in hypophysectomized rats by simulating different plasma patterns of GH. The results suggest that high, infrequent GH pulses with low plasma GH levels in between (i.e. a masculine plasma GH pattern) promotes growth more effectively than an intermediate, rather constant level of plasma GH (i.e. a feminine plasma GH pattern). Since male sex steroids masculinize the secretory pattern of GH and have only minor growth-promoting effects in hypophysectomized animals it appears that the growth promoting effect of androgens is indirect and is due to an altered secretory pattern of GH. Presumably, neonatal androgen secretion stimulates body growth during adult life by irreversibly masculinizing the secretory pattern of GH. In contrast, estrogens appear to influence body growth by mechanisms that are mainly independent of the secretory pattern of GH. Evidence is accumulating that the secretory pattern of GH in the rat also affects various sexually differentiated hepatic characteristics such as steroid metabolism and prolactin receptor concentration. Thus, a feminization of the liver develops after continuous, but not intermittent, administration of GH to hypophysectomized rats. GH secretion is predominantly regulated by two hypothalamic peptides; GRF, and the GH-release-inhibiting factor, somatostatin.(ABSTRACT TRUNCATED AT 400 WORDS)

In a double blind, cross-over placebo-controlled trial, we studied the effects of 26 weeks of replacement therapy with recombinant human GH on body composition, metabolic parameters, and well-being in 10 patients with adult-onset GH deficiency (GHD). All patients received appropriate thyroid, adrenal, and gonadal replacement therapy. The dose of recombinant human GH was 0.25-0.5 U/kg.week (0.013-0.026 mg/kg.day) and was administered sc daily at bedtime. One patient was withdrawn from the study because of edema and atrial fibrillation. Body composition was estimated with three independent methods: computed tomography, bioelectric impedance, and total body potassium combined with total body water assessments. The Comprehensive Psychological Rating Scale and the Symptom Check List-90 were used to assess any change in psychopathology. After 26 weeks of treatment, adipose tissue (AT) mass decreased 4.7 kg (P < 0.001). Subcutaneous AT decreased by an average of 13%, whereas visceral AT was reduced by 30%. Muscle volume increased by 2.5 kg (5%; P < 0.05). According to the four-compartment model derived from assessments of total body potassium and total body water, body cell mass and extracellular fluid volume increased significantly by 1.6 and 3.0 kg, whereas body fat decreased by 6.1 kg. Results obtained by the bioelectric impedance technique were similar. The mean (+/- SD) concentrations of insulin-like growth factor-I increased from 0.26 (0.06) at baseline to 2.56 (1.55) and 2.09 (1.03) kU/L after 6 and 26 weeks of treatment. Calcium and serum phosphate, osteocalcin, and procollagen-III concentrations were significantly higher, and intact PTH concentrations were reduced after 6 and 26 weeks of treatment, respectively. Total and free T3 concentrations were significantly increased after 6 and 26 weeks of treatment, whereas free T4 concentrations were reduced at 6 weeks, but after 26 weeks, free T4 concentrations had returned to pretreatment values. Finally, after 26 weeks of treatment, there was a decrease in the Comprehensive Psychological Rating Scale score (P < 0.05). The results show that GH replacement in GHD adults results in marked alterations in body composition, fat distribution, and bone and mineral metabolism and reduces psychiatric symptoms. Finally, we conclude that the observed beneficial effects of replacement therapy with GH are of sufficient magnitude to consider treatment of GHD adults.

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Rosén T, Edén S, Larson G. Wilhelmsen L, Bengtsson B-Â. Cardiovascular risk factors in adult patients with growth hormone deficiency. Acta Endocrinol 1993:129:195-200. ISSN 0001-5598 Patients with adult onset growth hormone deficiency have a decreased life expectancy owing to an increased mortality from cardiovascular disease. In the present study, 104 subjects (66 men and 38 women, aged 22\p=n-\74years) with growth hormone deficiency and with adequate replacement therapy with glucocorticoids, thyroid hormones and gonadal steroids were studied with respect to known risk factors for cardiovascular disease. For comparison, data from a population study, "the MONICA study", were obtained. The patients had a significantly higher body mass index compared to controls (p<0.001). Serum triglyceride concentration was higher (p<0.001) but there was no difference in serum total cholesterol concentration. Serum high-density lipoprotein cholesterol concentration was lower (p<0.001) in the patients. There was no difference in the prevalence of diabetes mellitus. The prevalence of treated hypertension was higher (p<0.05) in the patients but the prevalence of smoking was lower (p <0.001). Even after taking the increased body mass index into consideration, the changes in the prevalence of treated hypertension (p<0.05) and in the serum concentrations of triglycerides (p<0.05) and high-density lipoprotein concentrations (p<0.001) remained. These results indicate that growth hormone deficiency alters lipoprotein metabolism and increases the risk for development of hypertension, which in turn might contribute to the increased risk for cardiovascular disease.

The effects of growth hormone treatment of adults with adult-onset pituitary insufficiency on lipoproteins and apolipoproteins were investigated. Nine patients, one women and eight men (age range, 34-58 years), who had been treated for pituitary tumors were studied. They had complete pituitary insufficiency with a duration of at least 1 year. All patients received replacement therapy with thyroid hormones, glucocorticoids, and gonadal steroids. The study had a double-blind, placebo-controlled, crossover design for active treatment with recombinant human growth hormone (0.25-0.5 units/kg per week s.c given each evening) for 6 months. Fasting serum levels of cholesterol; triglycerides; high density lipoprotein and low density lipoprotein cholesterol; apolipoproteins A-I, B, and E; and lipoprotein (a) were measured before and after 6 and 26 weeks of treatment Lipoprotein (a) concentrations increased markedly during treatment and were about twice as high compared with pretreatment levels. Serum cholesterol and low density lipoprotein cholesterol concentrations were decreased after 6 weeks of treatment, but levels had returned to pretreatment levels after 26 weeks. High density lipoprotein cholesterol concentrations increased during treatment and were significantly higher than pretreatment levels after 26 weeks of treatment Serum trigiyceride concentrations did not change significantly, but in two patients with marked hypertriglyceridemia, growth hormone treatment resulted in a marked decrease. Serum concentrations of apolipoproteins A-I, B, and E did not change significantly, but changes in apolipoprotein A-I and B concentrations were in parallel to those observed for high density lipoprotein cholesterol and low density lipoprotein cholesterol, respectively. These results suggest that growth hormone is a major regulator of lipoprotein metabolism and also demonstrate that lipoprotein (a) concentrations are regulated by growth hormone. (Arteriosclerosis and Thrombosis 1993;13:296-301) KEY WORDS • lipoproteins • growth hormone • hypopituitarism F ew human studies have been performed on the effects of growth hormone (GH) on the different lipoprotein fractions and apolipoprotein levels. Moreover, studies on the effects of GH on the regulation of serum lipid levels have given conflicting results. However, both GH excess, as in acromegaly, 1 and deficiency 2 result in an increased risk of death due to cardiovascular disorders, which might indicate a role for GH in the control of lipoprotein metabolism in humans.Several recent publications have reviewed the genetics, biochemistry, and possible role in arteriosclerosis and thrombogenesis of lipoprotein (a) (Lp[a]). 3~6 The plasma concentration of Lp(a) is mainly genetically From the Department of Physiology (S.E., J.O.), the