As a general rule, hypothalamic neuropeptides that stimulate food intake act to inhibit the reproductive axis. We have studied the functions of two peptide systems in detail. Melanocortins, such as melanocyte stimulating hormone-α, β and γ, are products of the pro-opiomelanocortin (POMC) gene, produced in cells of the arcuate nucleus and act to inhibit feeding. Melanocortins also stimulate the reproductive axis. In lean hypogonadotropic ovariectomised ewes, POMC gene expression is reduced, but i.c.v. infusion of leptin increases expression of this gene and peptide levels as well as restoring pulsatile LH secretion. I.c.v. infusion of a melanocortin receptor agonist also increases LH secretion in lean animals, suggesting that the melanocortin system may be the means by which the reproductive axis is regulated by changing metabolic state. Furthermore, the agonist can stimulate pulsatile LH secretion in the luteal phase of the estrous cycle. Melanocortin cells have reciprocal communication with kisspeptin cells of the arcuate nucleus, so effects of these two systems on the GnRH cells may be integrated.
Gonadotropin inhibitory hormone (GnIH) is produced by cells of the dorsomedial hypothalamic nucleus/paraventricular nucleus. These cells project to GnRH cells and appetite regulating cells as well as to the neurosecretory zone of the median eminence. In sheep at least, GnIH acts to inhibit both GnRH cells and pituitary gonadotropes. The peptide also has a potent effect to stimulate food intake. GnIH gene expression is reduced in the periovulatory period, consistent with data from other species showing a reduction in appetite at the time of ovulation. Thus, GnIH signals to inhibit reproduction and stimulate food intake.
The melanocortins and GnIH both act to regulate reproduction and food intake. Reduced melanocortin levels in lean condition may be the cause of lowered activity of the reproductive axis.