Effects of six-month administration of recombinant human growth hormone to healthy elderly subjects.

In aging, both changes in body composition and a decrease in GH secretion are observed. While recombinant human GH (rhGH) therapy was shown to be effective in GH-deficient adults, its effects on normal aging are controversial. This study addressed the effects of six-month administration of low dosages of rhGH in a group of 5 healthy elderly subjects (age range 71-86 years). All subjects received 2 IU rhGH (Saizen, Serono) x 2/week s.c., which was approximately 0.03 mg/kg/week, and were examined before and 1, 3, and 6 months after the start of the therapy, as well as 3 months after therapy was suspended. Hormonal, metabolic and biochemical parameters, as well as bone density at the forearm level, body composition and muscle strength, assessed by isokinetic exercises, were evaluated at each scheduled visit. After the start of the therapy, there was an average 9 +/- 3% increase (median 8%) in IGF-I levels (IGF-I basal: 145.6 +/- 9 ng/mL, IGF-I peak: 176.0 +/- 10; p < 0.001). An increase in lean body weight, a decrease in fat (p < 0.05), and an improvement in muscle strength (p < 0.01) were recorded. No significant variation was observed in the metabolic parameters. During rhGH therapy, an increase in both bone resorption and formation parameters, and a slightly decreasing trend in bone density were noted. In conclusion, low dosages of rhGH in healthy elderly subjects seem to determine some physiological effects, such as a slight increase in IGF-I levels, which in turn may be responsible for the positive effects on body mass composition and muscle strength, without producing side effects. On the other hand, 6-month subcutaneous rhGH therapy at the dosage employed was unable to improve bone density.

Effect of cholinergic tone on growth hormone-releasing hormone-induced secretion of growth hormone in normal aging.

Aging is associated with an impairment in the GH response to GHRH and to several other stimuli of GH secretion. We evaluated the effect of pyridostigmine (PD) or placebo pretreatment (Protocol A: placebo or 120 mg PD orally at 8 a.m.; Protocol B: placebo or 60 mg PD twice orally at 9 p.m. and 7 a.m.) on GH responsiveness to GHRH (1 micrograms/kg BW bolus i.v. at 9 a.m.) in 15 normal elderly males (65-92 years) and in 14 normal young adults (20-37 years). GH response to GHRH was significantly reduced in elderly subjects compared to young adults (p < 0.05). PD (Protocol A) increased GH release in both elderly and young subjects. In elderly men, PD enhanced GH response to GHRH. The phenomenon was more evident when PD was administered according to Protocol B (p < 0.01). The area under the curve of GH was significantly greater after PD plus GHRH than it was after placebo plus GHRH (p < 0.01). In young adults, PD induced an increase in GH responsiveness to GHRH when administered according to Protocol A (p < 0.05) but not Protocol B. Both GH peak and AUC of GH after PD plus GHRH (Protocols A and B) in elderly subjects were not significantly different from the same parameters found in young subjects after placebo plus GHRH. Our data confirm that pituitary somatotrophin responsiveness to GHRH in man changes with aging. PD restores GH responsiveness to GHRH in elderly subjects. The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging.(ABSTRACT TRUNCATED AT 250 WORDS)

Growth hormone secretion in aging. Effect of pyridostigmine on growth hormone responsiveness to growth hormone-releasing hormone.

Recent studies in adults have shown that cholinergic enhancement by pyridostigmine (PD) has a stimulatory effect on growth hormone (GH) response to GH-releasing hormone (GHRH). PD probably reduces somatostatin release from the hypothalamus by increasing the central cholinergic tone. The aim of this study was to evaluate the effect of PD (120 mg orally) or placebo pretreatment on GH responsiveness to GHRH (1 micrograms/kg b.w. i.v.) or placebo in 10 normal elderly males (68-92 years). PD induced a significant increase in GH secretion (GH peak 7.3 +/- 1.8 micrograms/L, mean +/- SEM) over the basal value (0.9 +/- 0.2 micrograms/L; P less than 0.01) and enhanced GH response to GHRH (peak after GHRH: 17.0 +/- 3.8 micrograms/L; after PD plus GHRH: 42.6 +/- 12.2 micrograms/L; P less than 0.05). There was a significant difference in the secretory areas of GH among tests (P less than 0.05). The secretory area was greater after PD plus GHRH (2722 +/- 801 micrograms/L/120 min) than after GHRH (1185 +/- 206 micrograms/L 120 min; P less than 0.01). The effect of PD on GH secretion suggests that cholinergic mechanisms may be involved in GH control in normal aging. During the life-span cholinergic neurons and/or the somatostatin pathways could exert a differential effect on GH control.

Role of aging on growth hormone and prolactin release after growth hormone-releasing hormone and domperidone in man.

Growth hormone (GH) and prolactin (PRL) secretion after GH-releasing hormone (GHRH) and domperidone (DOM), an antidopaminergic drug which does not cross the blood-brain barrier (BBB), was evaluated in 8 healthy elderly men (65-91 years) and in 7 young adults (23-40 years). All received in random order at 2-day intervals: GHRH(1-40) (50 micrograms i.v.) bolus, DOM (5 mg/h) infusion, GHRH(1-40) (50 micrograms i.v.) plus DOM (5 mg/h i.v.), saline solution. In elderly men GH increase after GHRH was significantly lower than in young men. DOM alone did not change GH secretion in either of these groups, whereas it increased the GH response to GHRH only in young adults. PRL levels increased in both young and elderly men during both DOM and GHRH plus DOM, but the PRL release was more marked in young than in elderly men. Both integrated secretion of GH after GHRH and of PRL after DOM were inversely correlated to chronological age. Our data show an impairment of GH rise after GHRH and of PRL after DOM in elderly adults. It is also stressed that peripheral blockade of dopamine receptors by DOM is unable to amplify the GH response to GHRH only in elderly men. A reduction in GH release after GHRH might be related to aging, perhaps through a reduction of dopaminergic tonus.

[Study of the changes of some biohumoral parameters related to hepatic function. Special reference to the lipid pattern after treatment with alpha-mercaptopropionylglycine in a group of aged subjects]. / Studio delle variazioni di alcuni parametri bioumorali attinenti alla funzionalità epatica. Particolare riferimento al quadro lipidico, dopo trattamento con alpha-mercaptopropionilglicina in un gruppo di soggetti in età geriatrica.

A double-blind trial of alpha-mercaptopropionylglycine (1500 mg/day per os) against a placebo was run in 40 aged subjects. Liver function parameters and lipid and sugar metabolism were evaluated before and after the test. The results are discussed, with particular reference to those relating to lipid metabolism.