Seminar: "Gonadotropin Re-routing and Ovarian Function" -T. Rajendra Kumar

Dept. of Animal Sciences 

"Gonadotropin Re-routing and Ovarian Function"

T. Rajendra Kumar, MSc, MPhil, PhD

Professor & Edgar L, Patricia M Makowski and Family Endowed Chair; Director of the Women’s Reproductive Health Research Program

Department of Obstetrics & Gynecology, University of Colorado

The gonadotropic hormones, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) are heterodimers, synthesized in gonadotropes and regulated by gonadotropin releasing hormone. Yet, they have evolved distinct modes of cellular secretion. LH is secreted as pulses from the regulated release pathway while FSH is constitutively secreted. Why this hormone-specific pattern has evolved and whether the target organ, the ovary, senses specific hormone release pattern as a distinct signal input is not understood. We have engineered mice in which the intracellular trafficking and secretion pattern of gonadotropic hormones are genetically re-routed. Our in vivo approach allowed us to analyse the ovarian responses to altered patterns of gonadotropin signalling and the resulting ovarian phenotypes. The ability to modify the secretory fate of proteins in vivo has pathophysiological significance and could explain the etiology of several hormone hyperstimulation and resistance syndromes. Our studies also provide a molecular basis for the evolution of distinct patterns of gonadotropin secretion and may explain the origin of oestrus cycles in mammals.