GALANIN IS A PARACRINE INHIBITOR OF GONADOTROPH FUNCTION IN THE FEMALE RAT

Recent evidence suggests that pituitary galanin synthesized in the lac totroph is a paracrine regulator of lactotroph proliferation and PRL s ecretion and that these effects are mediated via a pituitary-specific galanin receptor, GAL-RB(orig.). At this receptor subtype, the, galani n fragment 3-29 is fully active, in contrast to both the cloned GAL-R1 and GAL-RE, at which this fragment is inactive. Since paracrine commu nication has been demonstrated between pituitary gonadotrophs and lact otrophs, we investigated the hypothesis that galanin is also a paracri ne regulator of gonadotroph function. Galanin attenuated LHRH-stimulat ed LH release in a dose-dependent manner in monodispersed rat anterior pituitaries harvested at proestrus (LHRH 100 nM, 10.7 +/- 0.2 ng/ml(- 1). 4 h vs. LHRH 100 nM + 1 mu M porcine galanin (pGal), 7.0 +/- 0.2 n g/ml(-1). 4 h; P < 0.01; i.e. 37% reduction). Galanin had similar supp ressive effects on FSH release. Galanin, also dose-dependently, attenu ated the LHRH-stimulated LH release from perifused proestrous rat pitu itary fragments. pGal (1 mu M) reduced the stimulated LH release by 80 %, [area under the curve (AUC), LHRH 100 nM, 713 +/- 149 vs. LHRH 100 nM + 1 mu M pGal, 131 +/- 7 ngl min . ml(-1 .)4 h; P < 0.02]. In addit ion, galanin 3-29, the specific GAL-R2(orig.) receptor agonist, inhibi ted LHRH-stimulated LH release from perifused proestrous rat pituitary fragments [AUC, LHRH 100 nM, 642 +/- 77 ng/min . ml(-1) vs. LHRH 100 nM + pGal 1-29, 206 +/- 44 ng/min . ml(-1) (P < 0.02); and LHRH 100 nM + pGal 3-29, 310 +/- 19 ng/min . ml(-1) (P < 0.02)]. Immunoblockade w ith specific galanin antiserum potentiated the LHRH-stimulated release of LH by 48% from perifused proestrous rat pituitary fragments (AUC, LHRH 100 nM + galanin antiserum, 721 +/- 65 ng/min . ml(-1) vs. LHRH 1 00 nM alone or with nonimmune antiserum, 489 +/- 33 ng/min . ml(-1) or 545 +/- 46 ng/min . ml(-1), P < 0.05). This data suggests that galani n may act as a paracrine agent via the pituitary-specific GAL-R2(orig. ) to inhibit gonadotroph function.