Seminar: "Regulation of Leydig Cell Steroidogenesis by Branched-Chain Amino Acid Metabolism and mTORC1-Mediated Translational Control" - Yeva Shamailova
Endocrinology and Animal Biosciences Dissertation Defense Seminar
This dissertation investigates how branched-chain amino acids (BCAAs) regulate Leydig cell steroidogenesis and male reproductive function. While Leydig cell steroidogenesis is traditionally viewed as primarily transcriptionally regulated by luteinizing hormone (LH), our study suggests that translational regulation also contributes to the rapid production of steroidogenic proteins and hormones. I first examined BCAA catabolism using a Bckdk mutant mouse model and primary mouse Leydig cells. Bckdk mutant males exhibited reduced circulating BCAA concentrations, impaired testosterone production, increased post-meiotic germ cell sloughing, and subfertility. In primary Leydig cells, leucine deprivation specifically impaired LH-stimulated testosterone production, demonstrating an important role for leucine in Leydig cell function. Next, I investigated the molecular mechanisms underlying rapid steroidogenesis using MA-10 Leydig cells. LH stimulation rapidly increased progesterone production and expression of steroidogenic proteins, including StAR and NR4A1. LH also activated mTORC1 signaling, while pharmacological inhibition of mTORC1 reduced steroid hormone production. Leucine deprivation similarly impaired LH-stimulated progesterone production. Together, these findings support a model in which BCAA availability and mTORC1-dependent translational regulation contribute to Leydig cell steroidogenesis, providing a potential mechanistic link between nutritional status, testosterone production, and male reproductive health.