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Endocrinology Vol. 139, No. 10 4222-4229
Copyright © 1998 by The Endocrine Society


ARTICLES

Galanin Is a Paracrine Inhibitor of Gonadotroph Function in the Female Rat

J. F. Todd1, C. J. Small2, K. O. Akinsanya, S. A. Stanley1, D. M. Smith and S. R. Bloom

Imperial College of Science, Technology and Medicine Endocrine Unit, Hammersmith Hospital, London W12 ONN, United Kingdom

Address all correspondence and requests for reprints to: Professor S. R. Bloom, ICSM Endocrine Unit, Hammersmith Hospital, Du Cane Road, London W12 ONN, United Kingdom. E-mail: sbloom{at}rpms.ac.uk

Recent evidence suggests that pituitary galanin synthesized in the lactotroph is a paracrine regulator of lactotroph proliferation and PRL secretion and that these effects are mediated via a pituitary-specific galanin receptor, GAL-R2(orig.). At this receptor subtype, the galanin fragment 3–29 is fully active, in contrast to both the cloned GAL-R1 and GAL-R2, at which this fragment is inactive. Since paracrine communication has been demonstrated between pituitary gonadotrophs and lactotrophs, we investigated the hypothesis that galanin is also a paracrine regulator of gonadotroph function. Galanin attenuated LHRH-stimulated 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 µM porcine galanin (pGal), 7.0 ± 0.2 ng/ml-1·4 h; P < 0.01; i.e. 37% reduction). Galanin had similar suppressive effects on FSH release. Galanin, also dose-dependently, attenuated the LHRH-stimulated LH release from perifused proestrous rat pituitary fragments. pGal (1 µM) reduced the stimulated LH release by 80%, [area under the curve (AUC), LHRH 100 nM, 713 ± 149 vs. LHRH 100 nM + 1 µM pGal, 131 ± 7 ng/min·ml-1·4 h; P < 0.02]. In addition, galanin 3–29, the specific GAL-R2(orig.) receptor agonist, inhibited 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 with 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 100 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 galanin may act as a paracrine agent via the pituitary-specific GAL-R2(orig.) to inhibit gonadotroph function.




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