Roles and mechanisms of action of nuclear receptors in steroidogenesis

睾丸间质细胞是男性体内主要的产生睾丸激素的细胞。这些细胞对于男性外生殖器的正常发育、性腺、肌肉质量的增加以及成熟精子的产生是必不可少的。间质细胞的功能受垂体黄体生成素（LH）的严格控制。LH与其位于间质细胞表面的受体结合，从而触发几个细胞内信号通路的激活（主要是cAMP/PKA通路），导致基因表达增加和类固醇激素的产生（甾体生成）。这些信号通路下游的转录因子及其作用机制仍然知之甚少。因此，目前研究计划的目标是确定这些因素并确定其作用机制。我认为在这一过程中发挥重要作用的转录因子家族是核受体家族，特别是NUR77和COUP-TFII。与我的假设一致，我们已经证明这些因素是类固醇基因表达的重要调节因子。我们也在分析NUR77表达本身是如何在各种刺激下被调节的。因此，不同但互补的最先进的分子和细胞生物学方法通常被用来阐明这个特殊的转录调节因子家族在lh诱导的性腺甾体生成中所起的作用，这是一个对男性生殖功能至关重要的过程。

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.