EVIDENCE FOR GNRH REGULATION BY LEPTIN - LEPTIN ADMINISTRATION PREVENTS REDUCED PULSATILE LH-SECRETION DURING FASTING

Administration of leptin during undernutrition improves reproductive f unction, but whether this occurs at the level of the brain, pituitary, or gonads is not yet clear. The present study tested the hypothesis t hat one important mechanism is the control of pulsatile gonadotropin-r eleasing hormone (GnRH) secretion. Our approach was to determine if le ptin could prevent the marked suppression of pulsatile luteinizing hor mone (LH) secretion which occurs during fasting. Leptin (3 mu g/g i.p. ; three times/48 h) or vehicle was administered during a 48-hour fast in adult ovariectomized and estrogen-treated ovariectomized rats (n = 5-7/group). LH was measured in blood samples collected every 6 min for 2 h before and after fasting. In vehicle-treated animals, plasma insu lin and leptin levels decreased after fasting. As expected, the LH pul se frequency also decreased markedly. When circulating leptin remained artificially elevated during fasting the suppression of LH pulse freq uency did not occur. Leptin treatment maintained a high LH pulse frequ ency in the presence or absence of estrogen. The finding that leptin m odulates LH pulse frequency indicates that this fat-derived hormone co nveys information about nutrition to mechanisms which regulate pulsati le gonadotropin-releasing hormone secretion. Because this occurs in th e absence of estrogen, the mechanism does not necessarily involve modu lation of negative feedback.