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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 329 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 329, 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 129, 206 ± 44 ng/min·ml-1 (P < 0.02); and LHRH 100 nM + pGal 329, 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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