The importance of peripheral nutritional signals to the functioning of the reproductive axis is appreciated, but the mechanisms are not well understood. The three tiers of the hypothalamic-pituitary-gonadal axis are receptive to many of these nutritional signals, including leptin. We have previously shown that leptin communicates with pituitary gonadotropes to maintain numbers of gonadotropin-releasing-hormone receptors (GnRHrs), and that loss of the leptin signal (LEPR) in gonadotropes results in subfertility in females. Using our current model of gonadotrope leptin resistance (GnRHR-cre, floxed Lepr exon 1) which targets the deletion of all LEPRs specifically to gonadotropes expressing Gnrhr, we investigated the role of leptin in the follicle-stimulating hormone (FSH) surge in female mice. Pituitaries and serum from 2-3 month-old control (CTL) and gonadotrope-Lepr-null (MUT) females were collected at midnight between proestrus and estrus, and at 0400 and 0900 on the morning of estrus. The samples were assayed for LH and FSH, and pituitaries were also used to determine GnRHr levels (ELISA) and Lh, Fsh, and Gnrhr mRNA levels (qPCR). Our gonadotrope-Lepr-null females showed a dramatic decrease in serum FSH during the peak of FSH secretion (0400 estrus, CTL: 25.8 ng/mL ± 5.7, n=6, MUT: 6.9 ng/mL ± 0.8, n=5, p
