Gonadotropin rerouting and ovarian function – from mice to humans

May 1, 2025 @ 11:00 am to 12:00 pm

T. Rajendra Kumar, PhD, University of Colorado

106 Animal, Veterinary, and Biomedical Sciences Building
University Park

T. Rajendra Kumar, PhD

Edgar L, Patricia M Makowski and Family Endowed Chair
Director, Women’s Reproductive Health Research
Division of Reproductive Sciences
Division of Reproductive Endocrinology and Infertility
Department of Obstetrics & Gynecology
University of Colorado Anschutz Medical Campus

“Gonadotropin rerouting and ovarian function – from mice to humans”

Abstract: Both the pituitary gonadotropic hormones, follicle-stimulating hormone (FSH) and luteinizing hormone (LH) are heterodimers (they share a common alpha subunit), are synthesized in gonadotrophs 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 in many species is constitutively secreted. The evolutionary significance of why this hormone-specific pattern has evolved and whether the target organ in the female, 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 rerouted. Our in vivo approach allowed us to systematically analyze the ovarian responses to altered patterns of gonadotropin signaling. These include identification of novel gene/protein networks and interesting ovarian phenotypes. The gonadotropin rerouting principle is currently being tested in the clinic to treat sub- and infertility in women. 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 genetic studies of rerouting also provide a molecular basis for the evolution of distinct patterns of gonadotropin secretion and may explain the origin of oestrus cycles in mammals.

Biography: Dr. T. Rajendra (Raj) Kumar is a tenured professor and The Edgar L, Patricia M Makowski and Family Endowed

Chair and Associate Vice-Chair of Research in the Department of Obstetrics & Gynecology at the University of Colorado Anschutz Medical Campus, Aurora. He is the Director of the Women’s Reproductive Health Research Program. He received his MS (Biochemistry), MPhil (Reproductive Physiology) from University of Hyderabad and PhD (Endocrine Biochemistry) from University of Delhi, India. He obtained his postdoctoral training at the Vollum Institute for Advanced Biomedical Research, Oregon Health Sciences University, Portland, OR and at Baylor College of Medicine, Houston, TX. He became an independent faculty at Baylor College of Medicine and then moved to University of Kansas Medical Center where he became a tenured professor and Director, Center for Reproductive Sciences. In 2016, he moved to University of Colorado Anschutz Medical Campus. Raj’s research focus has been on understanding gonadotrope tumors, gonadotropin biosynthesis, trafficking and secretion and actions in gonad development and gonadal and extragonadal physiology using mouse genetic

models. He published 150 papers, some of them in very high impact journals including Nature, Nature Genetics, Cell, Nature Communications, J Clinical Investigation, PNAS, Clinical Cancer Research, Molecular and Cellular Biology, Biology of Reproduction, Molecular Endocrinology and Endocrinology. He co-edited a textbook entitled “Transgenics in Endocrinology” and edited a textbook on “Gonadotropins: From Bench to the Bedside”. He is an Associate Editor of Biology of Reproduction, an Associate Editor of Molecular Reproduction and Development and a Reviewing Editor of Endocrinology. He has been an invited speaker at more than 180 national / international symposia and institutes all over the world. Dr. Kumar served as an Ad-hoc Member on several NIH Study Section and Special Emphasis review panels and as a standing member on the NIH-Integrative and Clinical and Endocrinology and Reproduction Review Panel (2019-2023). He has mentored over 100 members including junior faculty, postdoctoral and clinical fellows, graduate students, technicians and serves as a member on many graduate student thesis committees.

Raj received the University of Kansas (KU) - IDeA Network of Biomedical Research Excellence, Faculty Scholar Award, KU Medical Center Faculty Investigator Research Award and Thomas L. Noffsinger Investigator Award, Outstanding Reviewer Awards from the Endocrine Society and from Elsevier Press journal, Molecular and Cellular Endocrinology. He is the recipient of many awards including the 2018 Joy Goodwin Lecture (Auburn University), 2021 Neena B. Schwartz Memorial Keynote Lecture (Northwestern University) and the 2021 Janice E. Bahr Keynote Lectureship Award in Reproductive Biology (University of Illinois Urbana-Champaign), the 2021 David Yawn Commemorative Lecture Award (Baylor College of Medicine) and the 2025 The Hill Endowed Lecture (Penn State University) award. In 2025, he received the prestigious INRAe Professorship award form Le Studium, France. In 2022, he was elected to serve on the Board of Directors of the Society for the Study of Reproduction (2022-2025). He serves as an External Advisory Board Member to Center for Reproductive Sciences, Northwestern University and The Harvard Endocrine Unit, Mass General Hospital.