INTERACTION BETWEEN PROLACTIN AND CATECHOLAMINES ON HYPOTHALAMIC GNRHRELEASE IN-VITRO

Brain catecholamines have been implicated in the regulation of gonadot rophin release. It has been recently reported that noradrenaline (NA), applied within the hypothalamic paraventricular nucleus, suppresses t he pulsatile release of LH in the rat through a corticotrophin-releasi ng hormone (CRH)-dependent mecharism. Prolactin (PRL) is also able to suppress hypothalamic GnRH release following activation of the CRH-rel easing neurone. Given that PRL stimulates the release of NA from hypot halamic explants and that NA stimulates the release of hypothalamic CR H, we hypothesized that this neurotransmitter may be involved in the i ntrahypothalamic neuroendocrine circuit mediating the inhibitory effec ts of PRL on GnRH release. To test this hypothesis, we evaluated the e ffects of PRL on GnRH release in the presence of alpha- or beta-adrene rgic receptor antagonists using a static hypothalamic organ culture sy stem which enabled us to evaluate immunoreactive GnRH (iGnRH) release from individually incubated, longitudinally halved hypothalami. As pre viously shown, PRL at a concentration of 100 M inhibited basal iGnRH r elease by about 35%. Phentolamine, a non-selective alpha-adrenergic re ceptor antagonist, prazosin, an alpha(1)-receptor antagonist, and yohi mbine, an alpha(2)-receptor antagonist, overcame the inhibitory effect of PRL on iGnRH release in a concentration-dependent fashion. In cont rast, propranolol, a non-selective beta-adrenergic receptor antagonist , atenolol, a beta(1)-receptor antagonist, and ICI-118,551, a beta(2)- receptor antagonist, had no effect. None of these compounds had any ef fect on basal iGnRH release. These findings suggested that an alpha-ad renergic mechanism is involved in the suppressive effects of PRL on Gn RH release. Since the activation of alpha-adrenergic receptors increas es hypothalamic CRH release, we evaluated whether PRL stimulates CRH r elease via an alpha-adrenergic mechanism. PRL stimulated basal CRH rel ease by about twofold and this effect was inhibited by phentolamine in a concentration-dependent fashion. In conclusion, alpha-, but not bet a-, adrenergic receptors mediate the inhibitory effects of PRL on GnRH release in vitro. We speculate that, at least under these experimenta l conditions, PRL inhibits GnRH release through an alpha-adrenergic me chanism which activates the CRH-secreting neurone.