Leptin and ciliary neurotropic factor (CNTF) inhibit fasting-induced suppression of luteinizing hormone release in rats: role of neuropeptide Y.

Periods of chronic undernutrition and short periods of fasting suppress pituitary luteinizing hormone (LH) secretion and upregulate hypothalamic neuropeptide Y (NPY), the orexigenic peptide. The effect of suppression of NPY upregulation with ciliary neurotropic factor (CNTF), a cytokine, and leptin, an adipocyte hormone, on pituitary LH secretion was evaluated in fasted rats. In the first experiment, daily injection of CNTF (0.2 nmol) intracerebroventricularly (i.c.v.) for 4 days drastically reduced food intake and body weight gain similar to the weight loss seen in pair-fed rats. Food deprivation (FD) also decreased body weight. Despite drastic loss in body weight, plasma LH was reduced in FD and pair-fed rats, but not in CNTF-treated rats. In the second experiment, FD rats received either control vehicle, CNTF (0.2 nmol) or leptin (0.2 nmol) daily for 4 days. FD increased steady state levels of preproNPY mRNA in the hypothalamus over the control freely-fed rats. However, both CNTF and leptin suppressed hypothalamic gene expression and significantly attenuated LH suppression in response to FD. Taken together, these results support the hypothesis that the upregulation of hypothalamic NPY system may underlie diminution in pituitary gonadotropin secretion and that the NPYergic pathway may serve as a communication bridge between the neural processes that regulate reproduction and those that maintain energy balance.