INHIBITORY EFFECT OF AMYLIN ON GROWTH-HORMONE RESPONSIVENESS TO GROWTH-HORMONE-RELEASING HORMONE IN THE RAT

The effects of intracerebroventricular (i.c.v.) or intracarotid (i.a.) administration of amylin (AMY) on growth hormone (GH) release induced by GH-releasing hormone (GHRH) were examined in conscious male rats. Amylin (25 ng-5 mu g/rat, i.c.v. or 10 mu g/rat, i.a.) was administere d 10 min before GHRH (2 mu g/kg, i.a.). I.c.v. administration of AMY d ose-dependently inhibited GH secretion induced by GHRH but when given peripherally, AMY did not modify the GH response to GHRH. Amylin (10(- 8)-10(-6) M) had no direct effect on the rat anterior pituitary in vit ro either alone or when incubated with GHRH. To characterize the mecha nism(s) involved in vivo in the inhibition of GH by AMY, we examined, at first, the effects of AMY on GHRH-induced GH release in rats deplet ed of somatostatin by pretreatment (4 h before) with cysteamine (300 m g/kg s.c.). The inhibitory activity of AMY on GH secretion elicited by GHRH seems to be independent of hypothalamic somatostatin; in fact, A MY was still active in rats treated with cysteamine. In addition, we e xamined the effects of i.c.v. AMY administration on clonidine (CLO)-in duced GH secretion and on dopamine and noradrenaline content in the br ain, since it is known that GHRH is a stimulus sensitive to changes in central catecholaminergic activity. The failure of AMY to affect GH s ecretion induced by activation of postsynaptic alpha(2)-receptors by C LO and the finding that the peptide decreased noradrenaline content in the hypothalamus and striatum, indicates that AMY may inhibit GH rele ase by interfering with the facilitatory influence of hte catecholamin ergic system on GH secretion.