Towards Curative Therapies for Hypogonadotropic Diseases

PROJECT ABSTRACT Kisspeptin, neurokinin B, and dynorphin signaling provide essential guidance and stimulation to GnRH neurons. Though the past decade has seen extraordinary advances in our understanding of this signaling network, this grant employs novel assays and receptor agonist and antagonist administration in vivo to challenge several dogmas in reproductive endocrinology. These complementary approaches, performed in rhesus monkeys, healthy volunteers, and patients with reproductive disease, unite two investigators with experience in genetics, physiology, and pharmacology. This interdisciplinary collaboration is well positioned to attack the complexities of the hypothalamic architecture that regulates GnRH secretion. Thus, by translating fluidly between monkey and man, between juvenile and adult, and between physiology and pathophysiology, this grant aims to generate novel insights into sexual maturation and develop new treatments for patients with reproductive disorders.