THE STIMULATORY EFFECT OF LEPTIN ON THE NEUROENDOCRINE REPRODUCTIVE AXIS OF THE MONKEY

Leptin acts as a metabolic activator of the neuroendocrine reproductiv e axis in several rodent species, but whether leptin plays a similar r ole in primates is unknown. To explore this question, we examined the effects of leptin on gonadotropin and testosterone secretion in male r hesus monkeys that were fasted for 2 days. Mean plasma levels of LH an d FSH, LH pulse frequency, and LH pulse amplitude were significantly h igher in leptin-treated animals compared with saline-treated controls during the second day of the fast. To identify targets for leptin's ac tion, we used in situ hybridization and computerized imaging to map le ptin receptor (Ob-R) messenger RNA (mRNA) distribution. Ob-R mRNA was observed in the anterior pituitary and several areas of the brain, inc luding the arcuate and ventromedial nuclei of the hypothalamus. Ob-B m RNA was coexpressed in both POMC and neuropeptide Y neurons in the arc uate nucleus, whereas little or no coexpression of Ob-R mRNA was evide nt in GnRH neurons. These results suggest that leptin is a metabolic s ignal to the reproductive axis in primates and imply that both POMC an d neuropeptide Y neurons are involved in mediating leptin's effects in the brain.