Roles and mechanisms of action of nuclear receptors in steroidogenesis

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Testicular Leydig cells are the main testosterone-producing cells in the male. These cells are indispensable for the proper development of external male genitalia, sex accessory glands, increased muscle mass, as well as production of mature sperm. Leydig cell function is tightly controlled by the pituitary luteinizing hormone (LH). LH binds to its receptor located on the surface of Leydig cells thus triggering activation of the several intracellular signaling pathways (the main one being the cAMP/PKA pathway) leading to increased gene expression and steroid hormone production (steroidogenesis). The transcription factors downstream of these signaling pathways and their mechanisms of action remain poorly understood. Therefore, the goal of the present research program is to identify these factors and to determine their mechanism of action. One family of transcription factors that I believe play an important role in this process is nuclear receptor family, particularly NUR77 and COUP-TFII. Consistent with my hypothesis, we have shown that these factors are important regulators of steroidogenic gene expression. We are also analyzing how NUR77 expression itself is regulated in response to the various stimuli. Thus, different but complementary state-of-the-art molecular and cellular biology approaches are routinely used to elucidate the roles played by this particular family of transcriptional regulators in LH-induced gonadal steroidogenesis, a process critical for male reproductive function.