Endocrine Abstracts

Galanin-like peptide (GALP) is a novel peptide isolated from the porcine hypothalamus. Within the hypothalamus GALP mRNA is confined to the arcuate nucleus from which GALP immunoreactive fibres project to the medial preoptic area. Previous studies indicate that GALP may be regulated by leptin. Intracerebroventricular administration of GALP has been shown to stimulate luteinising hormone release. Low circulating levels of leptin lead to the down regulation of the hypothalamic-pituitary-gonadal axis (HPG). Taken together these findings suggest that GALP could play an intermediary role in coupling the action of leptin to the HPG.
In the present study we have employed a static hypothalamic explant system to examine the effects of leptin on GALP release and the effects of GALP on GnRH release. In addition we have investigated the effects of GALP directly on GnRH neurons through the use of the immortalized hypothalamic GnRH clonal cell line, GT1-7. Leptin (100 nanomolar) significantly increased the release of GALP from hypothalamic explants (basal 4.26 plus/minus 0.30 nanograms per explant, leptin 5.25 plus/minus 0.33 nanograms per explant, p<0.01, n=18). GALP (100 nanomolar) significantly increased the release of GnRH from hypothalamic explants (basal 8.1 plus/minus 2.3 fentomoles per explant; GALP 18.2 plus/minus 2.3 fentomoles per explant, n=13, p<0.01). GALP also dose dependently increased the release of GnRH from GT1 7 cells (basal 8.3 plus/minus 0.6 fentomoles per well, 1 nanomolar GALP 13.4 plus/minus 1.0 fentomoles per well, 10 nanomolar GALP 16.4 plus/minus 1.0 fentomoles per well, n=12-20, p<0.001).
This data demonstrates in vitro, GALP stimulates the release of GnRH, at least partially, through a direct activation of GnRH neurons. In addition this study suggests GALP release within the hypothalamus may be modulated by leptin. These data support a role for GALP in mediating the effects of leptin on the HPG axis.