Extra-Ovarian Gonadotropin Negative Feedback Revealed by Aromatase Inhibition in Female Marmoset Monkeys

While the ovary produces the majority of estradiol (E2) in mature female primates, extra-ovarian sources contribute to E2 synthesis and action, including brain E2 regulating hypothalamic gonadotropin-releasing hormone (GnRH). In ovary-intact female rodent models, aromatase inhibition (AI) induces a PCOS-like hypergonadotropic hyperandrogenism due to absent E2-mediated negative feedback. In order to examine the role of extra-ovarian E2 on nonhuman primate gonadotropin regulation, the present study employs letrozole to elicit AI in adult female marmoset monkeys. Sixteen female marmosets (Callithrix jacchus) (>2yrs) were randomly assigned to ovary intact or ovariectomy (OVX) conditions and subsequently placed on a daily oral regimen of either ~200µl vehicle alone (ovary intact Control, n=3, OVX, n=3) or 1 mg/kg/day Letrozole in vehicle (ovary intact AI, n=4; OVX+AI, n=6). Blood samples were collected every 10 days and plasma chorionic gonadotropin (CG) and steroid hormone levels were determined by validated RIA and LC-MS/MS, respectively. Ovary intact AI-treated and OVX females exhibited elevated CG (p