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 [growth hormone] levels, but not PRL [prolactin] 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 .beta.-endorphin (10-10 and 10-9 mol) and D-[Ala2]enkephalin amide (10-9 mol) stimulated both GH and PRL release, whereas .alpha.- and .gamma.-endorphins, [Met5]lenkephalin and morphine sulfate (10-9 mol) induced only a meager GH response, but a significant PRL response. Simultaneous injection of .beta.-endorphin (10-10 or 10-9 mol) and substance P (10-9 mol) caused greater GH and PRL responses than did .beta.-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 .beta.-endorphin (10-10 mol), but also blocked the synergistic effect of substrate P on both GH and PRL responses to .beta.-endorphin. The intraventricular administration of substance P may stimulate hypothalamic somatostatin release into the portal vessels, thereby decreasing GH secretion. The opiate receptor activator stimulated GH and PRL release by a mechanism which does not involve endogenous somatostatin. Substance P may potentiate the action of opiate receptor stimulators on GH and PRL release in the CNS.