EFFECTS OF AMYLIN AND SALMON-CALCITONIN ON BETA-ENDORPHIN-INDUCED GROWTH-HORMONE AND PROLACTIN SECRETION IN THE RAT

In this study we examined the possible interplay of amylin (AMY) and s almon calcitonin (sCT) in the central control of growth hormone (GH) a nd prolactin (PRL) secretion in male rats. For this purpose we first c ompared effects of central intracerebroventricular (i.c.v.) administra tion of various doses of AMY (2.5-2,500 ng/rat) and sCT (2.2-220 ng/ra t) on beta-endorphin (beta-END, 0.5 mu g/rat)-induced GH and PRL secre tion. AMY and sCT dose-dependently inhibited beta-END-induced GH secre tion, whereas only sCT was able to inhibit beta-END-induced PRL secret ion. To examine whether the GH inhibitory effect of AMY was due to the possible cross-reactivity of AMY and sCT on the same receptors in the CNS, we pretreated some rats with the AMY antagonist (AMY(8-37), 2.5 mu g/rat, i.c.v.). AMY(8-37) significantly enhanced the GH-stimulatory action of beta-END. AMY(8-37), administered prior to AMY and sCT, sig nificantly removed the inhibitory effect of both AMY and sCT on beta-E ND-induced GH release, suggesting that both peptides mediate their res ponse on GH through a common receptor. In vitro competition binding st udies on rat hypothalamic membranes have shown that both AMY and sCT c ompete with [I-125]rAMY binding with half inhibition (IC50) values of 3.6 x 10(-11) and 1.6 x 10(-10) M, respectively. Binding of [I-125]sCT was inhibited by sCT with an IC50 of 1.09 x 10(-10) M and to a lesser extent by AMY with an IC50 of 1.3 x 10(-6) M. Thus it is possible tha t the two peptides recognize a common hypothalamic receptor but with d ifferent affinities (sCT > AMY). Overall these data indicate that AMY behaves as a mimic of sCT in the central control of GH secretion. The failure of AMY, at variance with sCT, to modify the PRL- releasing act ivity of beta-END indicates that different receptor subtypes for sCT a re involved in the endocrine effects of sCT and only those mediating t he modulatory action of GH respond to AMY.