RESUMO
Growth hormone secretion is classically modulated by two hypothalamic hormones, growth hormone-releasing hormone and somatostatin. A third pathway was proposed in the last decade, which involves the growth hormone secretagogues. Ghrelin is a novel acylated peptide which is produced mainly by the stomach. It is also synthesized in the hypothalamus and is present in several other tissues. This endogenous growth hormone secretagogue was discovered by reverse pharmacology when a group of synthetic growth hormone-releasing compounds was initially produced, leading to the isolation of an orphan receptor and, finally, to its endogenous ligand. Ghrelin binds to an active receptor to increase growth hormone release and food intake. It is still not known how hypothalamic and circulating ghrelin is involved in the control of growth hormone release. Endogenous ghrelin might act to amplify the basic pattern of growth hormone secretion, optimizing somatotroph responsiveness to growth hormone-releasing hormone. It may activate multiple interdependent intracellular pathways at the somatotroph, involving protein kinase C, protein kinase A and extracellular calcium systems. However, since ghrelin has a greater ability to release growth hormone in vivo, its main site of action is the hypothalamus. In the current review we summarize the available data on the: a) discovery of this peptide, b) mechanisms of action of growth hormone secretagogues and ghrelin and possible physiological role on growth hormone modulation, and c) regulation of growth hormone release in man after intravenous administration of these peptides.
Assuntos
Humanos , Hormônio Liberador de Hormônio do Crescimento/fisiologia , Hormônio do Crescimento Humano/fisiologia , Hormônios Peptídicos , Receptores Acoplados a Proteínas G/fisiologia , Grelina , Hormônio Liberador de Hormônio do Crescimento , Hormônio Liberador de Hormônio do Crescimento/uso terapêutico , Hormônio do Crescimento Humano , Hormônio do Crescimento Humano/uso terapêutico , Oligopeptídeos/fisiologia , Hormônios Peptídicos/fisiologia , Hormônios Peptídicos/uso terapêutico , Receptores de GrelinaRESUMO
1. A neuroendocrine role for calcitonin (CT) has been suggested by the finding of CT receptors in the hypothalamus. We have recently shown that salmon calcitonin (sCT) inhibits growth hormone releasing hormone (GHRH)-induced GH secretion in msn by a mechanism apparently independent of changes in peripheral cortisol, glucose, calcium or parathyroid levels. 2. We have further investigated the inhibitory action of sCT on GH secretion by studying the effects of sCT (100 MRC units, im) or placebo on basal and GHRH (1-29) NH2 (50µg, iv) stimulated GH secretion in 6 acromemgalic patients with active disease. 3. Basal GH lelvels were not altered by sCT administration (placebo: 136 ñ 99 µg/1 vs sCT: 99 ñ 53 µg/1). However, the GH response to GHRH was decreased by sCT. The area under the curve was signficantly smaller when patients were treated with sCT compared to placebo controls (placebo: 77202 ñ 57036 vs sCT: 64828 ñ 51909 µg min-1 1-1; P < 0.01). No changes in glucose or calcium levels were observed. 4 These results demonstrate that sCT decresases GHRH-induced GH secretion in acromegalic patients. Although the mechanism of action of sCT on GH secretion is unknown, our results indicate that the inhibitory effect of this peptide on GH secretion is also observed in patients harboring pituitary adenomas
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Acromegalia/fisiopatologia , Calcitonina/fisiologia , Hormônio Liberador de Hormônio do Crescimento/metabolismo , Somatostatina/metabolismo , Acromegalia/sangue , Calcitonina/administração & dosagem , Cálcio/sangue , Hormônio Liberador de Hormônio do Crescimento/farmacologiaRESUMO
Vasoactive intestinal polypeptide (VIP) is present in high concentrations in the hypothalamus and appears to be involved in the modulation of growth hormone (GH) secretion. The effects of VIP on huypothalamic somatostatin (SMS) release are, however, controversial. To further elucidate the mechanism of action of this peptide on GH secretion we studied the effects of VIP on SMS secretion from incubated rat hypothalamic fragments in vitro. At 10**6 M, VIP induced a significant increase in basal SMS release (P<0.01), whereas at 10**-10 M it had an inhibitory effect. We suggest that the increase in GH after in vivo administration of VIP may be modulated, at least in part, by a direct effect of this peptide on SMS neurons, while the stimulatory effect of high doses of VIP on SMS release may represent a pharmacological interaction of this peptide with growth hormone releasing hormone, peptide histidine isoleucine, or glucagon receptors