galanin-like-peptide and galantide

Galanin (Gal) and galanin-like peptide (GALP) may be involved in the mechanisms of the hypothalamo-neurohypophysial system. The aim of the present in vitro study was to compare the influence of Gal and GALP on vasopressin (AVP) and oxytocin (OT) release from isolated rat neurohypophysis (NH) or hypothalamo-neurohypophysial explants (Hth-NH). The effect of Gal/GALP on AVP/OT secretion was also studied in the presence of galantide, the non-selective galanin receptors antagonist. Gal at concentrations of 10(-10 )M and 10(-8 )M distinctly inhibited basal and K(+)-stimulated AVP release from the NH and Hth-NH explants, whereas Gal exerted a similar action on OT release only during basal incubation. Gal added to the incubation medium in the presence of galantide did not exert any action on the secretion of either neurohormone from NH and Hth-NH explants. GALP (10(-10 )M and 10(-9 )M) induced intensified basal AVP release from the NH and Hth-NH complex as well as the release of potassium-evoked AVP from the Hth-NH. The same effect of GALP has been observed in the presence of galantide. GALP added to basal incubation medium was the reason for stimulated OT release from the NH as well as from the Hth-NH explants. However, under potassium-stimulated conditions, OT release from the NH and Hth-NH complexes has been observed to be distinctly impaired. Galantide did not block this inhibitory effect of GALP on OT secretion. It may be concluded that: (i) Gal as well as GALP modulate AVP and OT release at every level of the hypothalamo-neurohypophysial system; (ii) Gal acts in the rat central nervous system as the inhibitory neuromodulator for AVP and OT release via its galanin receptors; (iii) the stimulatory effect of GALP on AVP and OT release is likely to be mediated via an unidentified specific GALP receptor(s).

Topics: Animals; Galanin; Galanin-Like Peptide; Hypothalamo-Hypophyseal System; Male; Oxytocin; Rats; Rats, Wistar; Receptors, Galanin; Substance P; Vasopressins

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.

Topics: Animals; Cell Line; Cell Line, Transformed; Culture Techniques; Galanin; Galanin-Like Peptide; Gene Expression; Gonadotropin-Releasing Hormone; Gonads; Hypothalamus; Immune Sera; Leptin; Male; Mice; Mice, Inbred CBA; Pituitary Gland; Rats; Rats, Wistar; Receptors, Galanin; Receptors, Leptin; Substance P