Harvard Catalyst Profiles

The biological mechanism that triggers puberty, marking the transition from childhood to adulthood, remains unknown. Together with my colleagues and collaborators, I have been researching the molecular genetic causes of failure to start puberty to gain insight into normal pubertal development. We and others seminally described inactivating mutations in the genes encoding for the hypothalamic neuropeptides Kisspeptin and Neurokinin B and their respective receptors in human patients who failed to start puberty. These discoveries were essential in the recent characterization of the Kisspeptin (KNDy) neurons in the hypothalamic infundibular (arcuate) nucleus as the Gonadotropin-Releasing Hormone (GnRH) pulse generator. The onset of puberty is marked by rhythmic kisspeptin secretion from the GnRH pulse generator, which stimulates the production of reproductive hormones. Our research aims to identify the mechanism that reactivates the GnRH pulse generator after a period of inactivity during childhood.