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 suppres s pituitary luteinizing hormone (LH) secretion and upregulate hypothal amic neuropeptide Y (NPY), the orexigenic peptide. The effect of suppr ession of NPY upregulation with ciliary neurotropic factor (CNTF), a c ytokine, and leptin, an adipocyte hormone, on pituitary LH secretion w as evaluated in fasted rats. In the first experiment, daily injection of CNTF (0.2 nmol) intracerebroventricularly (i.c.v.) for 4 days drast ically 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 expe riment, FD rats received either control vehicle, CNTF (0.2 nmol) or le ptin (0.2 nmol) daily for 4 days. FD increased steady state levels of preproNPY mRNA in the hypothalamus over the control freely-fed rats. H owever, both CNTF and leptin suppressed hypothalamic gene expression a nd significantly attenuated LH suppression in response to FD. Taken to gether, these results support the hypothesis that the upregulation of hypothalamic NPY system may underlie diminution in pituitary gonadotro pin secretion and that the NPYergic pathway may serve as a communicati on bridge between the neural processes that regulate reproduction and those that maintain energy balance. (C) 1998 Elsevier Science Ireland Ltd.