Activation of cyclic AMP second messenger system stimulates secretion of β-endorphin from fetal hypothalamic cells

Abstract

Relatively little is known about physiological regulators of hypothalamic β-endorphin (END) secretion and mechanisms by which they stimulate secretion. We sought to determine whether activation of the cyclic AMP (cAMP) second messenger pathway was involved in stimulating hypothalamic β-END secretion from dissociated fetal hypothalamic cells in culture. Forskolin (FSK), a direct activator of adenylate cyclase which stimulates cAMP formation, stimulated immunoreactive (IR)-β-END secretion. Because FSK can also stimulate independent of increased cAMP formation, we studied dibutyryl cAMP and 8-bromo-cAMP, analogues of cAMP, which also stimulated IR-β-END secretion. From these studies we conclude: (1) activation of the cAMP second messenger system stimulates IR-β-END secretion from hypothalamic cells and supports the rationale that endogenous regulators which stimulate this pathway could be involved in the physiological regulation of hypothalamic β-END secretion; (2) coupling between the cAMP second messenger pathway and stimulation of hypothalamic β-END secretion which is presumably present at maturity (adulthood) originates at early stages of development (fetal life).