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A. Kemal Topaloglu, M.D.

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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.

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Available: 08/05/24, Expires: 06/30/26

Mechanisms controlling the hypothalamic-pituitary-gonadal (HPG) axis throughout human life stages, including puberty, are unknown. Idiopathic hypogonadotropic hypogonadism (IHH) denotes the failure to start puberty due to central causes. Human genetic studies on IHH patients by our lab as well as others have led to the discovery of critical mediators of puberty, namely the neuropeptides kisspeptin and neurokinin B. These discoveries were instrumental in the characterization of the KNDy neurons as the GnRH pulse generator. However, the processes controlling the GnRH pulse generator in different life stages, including puberty, remain elusive. Visiting students would be an integral part of the ongoing intellectual discussion along with the hands-on molecular genetics and cellular lab activities aiming to elucidate the mechanism controlling pubertal development.


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© 2024 President and Fellows of Harvard College
Funded by the NIH National Center for Advancing Translational Sciences through its Clinical and Translational Science Awards Program, grant number UL1TR002541.