Molecular mechanisms and signal transduction pathways involved in regulation of steroidogenesis and adaptation of Leydig cells to disturbed homeostasis

Given the essential role of testosterone production for reproductive and other physiological function, a clear understanding of the intricate signaling molecules network coordinating Leydig cells function is crucial. Despite that, precise molecular mechanisms involved in regulation of steroidogenesis during disturb homeostasis (stress, application of anabolics, hypogonadal hypogonadism, metabolic syndrome, etc) are still missing. This project is designed to systematically analyze and characterize crucial molecular mechanisms and signaling pathways regulating the Leydig cells function in disturbed homeostasis of whole organism during prenatal life, childhood, puberty, adulthood and aging. Three different experimental approaches will be used: (1) In vivo models of disturbed homeostasis (1a. psycho-physical stress, 1b. in vivo application of anabolics 1c. hypogonadal hypogonadism) - to define possible mechanisms of Leydig cells adaptation; (2) Different models based of mouse functional genomics (2a. Igf1r/p450sccCre and 2b. Cyp51/AmrCre knock-out mice) - to characterize steroidogenic machinery function and regulation in disturbed homeostasis of growth factors and cholesterol; (3) In vitro models of primary cells cultures and corresponding immortalized cell lines (3a. hypothalamic neurons vs GT1-7 neurons, 3b. pituitary gonadotrophs vs alphaT3 cells, 3c. Leydig cells vs MA-10 cells) - to follow trafficking of specific signaling molecules and define protein/protein interactions.