Studies on the Interaction of Endorphins, Substance P, and Endogenous Somatostatin in Growth Hormone and Prolactin Release in Rats

Abstract

Substance P and various opiate receptor activators were injected into the lateral ventricle of urethane-anesthetized male rats which were pretreated with either normal sheep serum (NSS), sheep antiserum to somatostatin (anti-SS), or rabbit antiserum to substance P (anti-SP). The injection of substance P (10-9 mol) suppressed serum GH levels, but not PRL levels, in both NSS- and anti-SP-pretreated rats, whereas the suppressive effect was not observed in animals pretreated with anti-SS. In both NSS- and anti-SS-pretreated rats, β-endorphin (10-10 and 10-9 mol) and D-[Ala2]enkephalin amide (10-9 mol) stimulated both GH and PRL release, whereas α- and γ-endorphins, [Met5]enkephalin, and morphine sulfate (10-9 mol) induced only a meager GH response, but a significant PRL response. Simultaneous injection of β-endorphin (10-10 or 10-9 mol) and substance P (10-9 mol) caused greater GH and PRL responses than did β-endorphin alone in rats pretreated with either NSS, anti-SS, or anti-SP. Both GH and PRL responses to morphine sulfate (10-9 mol) plus substance P (10-9 mol) were larger than those to morphine sulfate alone. Naloxone (10-9 mol) not only inhibited both GH and PRL release induced by β-endorphin (10-10 mol), but also blocked the synergistic effect of substance P on both GH and PRL responses to β-endorphin. These results suggest the following: first, the intraventricular administration of substance P may stimulate hypothalamic somatostatin release into the portal vessels, thereby decreasing GH secretion; second, the opiate receptor activator stimulates GH and PRL release by a mechanism which does not involve endogenous somatostatin; third, substance P may potentiate the action of opiate receptor stimulators on GH and PRL release at the central nervous system. © 1978 by The Endocrine Society.