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Galanin-Like Peptide Stimulates the Release of Gonadotropin-Releasing Hormone in Vitro and May Mediate the Effects of Leptin on the Hypothalamo-Pituitary-Gonadal Axis

Division of Metabolic Medicine, Faculty of Medicine, Imperial College of Science, Technology and Medicine, Hammersmith Campus, London W12 ONN, United Kingdom

Address all correspondence and requests for reprints to: Professor S. Bloom, Division of Metabolic Medicine, Faculty of Medicine, Imperial College of Science Technology and Medicine, Hammersmith Campus, Du Cane Road, London W12 ONN, United Kingdom. E-mail: s.bloom{at}ic.ac.uk.

Leptin regulates the hypothalamo-pituitary-gonadal axis in relation to nutritional status. The mechanism through which leptin mediates its effects on neuroendocrine reproductive circuits remains unclear. Galanin-like peptide (GALP) is a recently identified hypothalamic peptide, localized in the arcuate nucleus, which seems to be regulated by leptin and stimulates LH when administered centrally. Here, we demonstrate that leptin stimulates the release of GALP and GnRH in vitro from hypothalamic explants harvested from male rats. In addition, we show that GALP stimulates the release of GnRH from hypothalamic explants and GT1–7 cells. Furthermore, we demonstrate that GALP antiserum blocks the stimulatory action of leptin on GnRH release from hypothalamic explants. GALP is a ligand of the galanin receptors. We therefore investigated whether the effect of GALP on GnRH release may be mediated via a known galanin receptor. GALP-stimulated GnRH release from hypothalamic explants was attenuated (but not abolished) by the galanin receptor antagonist galantide. However, GALP-stimulated GnRH release from GT1–7 cells was not diminished by the coadministration of galantide. In addition, none of the cloned galanin receptors were expressed in GT1–7 cells by RT-PCR. These observations suggest that GALP may stimulate GnRH release through an indirect pathway involving a galanin receptor and via a direct action on GnRH neurons, possibly through a novel receptor. These findings suggest that GALP may mediate the actions of leptin on the reproductive axis and provide a link between nutrition and fertility.

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