脂肪细胞因子chemerin及其受体在Leydig细胞中的表达及作用机制的研究

睾酮在雄性生殖中起关键作用，其中95%的睾酮由睾丸Leydig细胞分泌。但是影响Leydig细胞睾酮分泌的调控机理尚未完全清楚。近年来，人们发现多个脂肪细胞因子(如瘦素、脂联素、抵抗素)参与了睾酮分泌的调控。我们的前期实验结果表明新发现的脂肪细胞因子chemerin及其受体（CMKLR1、CCRL2和GPR1）的mRNA及蛋白在睾丸中，尤其是Leydig细胞中有高表达。据此我们提出假设：chemerin及其受体在Leydig细胞中可能具有重要的生理功能（如调控睾酮分泌）。我们将建立原代培养的Leydig细胞模型和LPS诱导的大鼠非典型睾丸炎动物模型，利用单抗、siRNA、受体拮抗剂等工具，在生理/病理条件下，深入研究chemerin及其受体在Leydig细胞中的生理学功能及信号通路，进一步阐明Leydig细胞睾酮分泌的调控机制，为探索雄激素缺陷导致的不孕不育的治疗提供新的思路。

Besides the classical hypothalamic-pituitary-gonadal axis control of testicular testosterone production, adipokines prove to be a new role player in it. Newly established as the biggest endocrine organ, adipose tissue secrets several endocrine adipokines: leptin, adiponectin and resistin. These three functions to regulate the testicular testosterone production. .Chemerin is a novel adipokine, with relevant roles in inflammation, lipid metabolism and glucose homeostasis. However, whether this novel adipokine is expressed and/or conducts biological actions in the male gonad reminds unexplored. Our preliminary data shows high gene expression of chemerin and its three receptors in the testis with strong and specific staining of one of the receptor GPR1 in the Leydig cells. We hypothesize that chemerin plays important roles in Leydig cells testosterone production directly through GPR1-dependent pathway. Considering the published anti- and pro-inflammatory roles of chemerin, together with the suppression effect of inflammation on testosterone production, we hypothesize that chemerin might also regulate testosterone production indirectly by acting either anti- or pro-inflammatory in the pathological condition of orchitis. .In this study, we will investigate the possible roles of chemerin in testosterone production by an in vitro model of rat primary Leydig cell culture and to decipher its corresponding receptor and pathway. We will also study the possible relationship between inflammation, chemerin and testosterone production by the in vivo model of LPS-induced rat orchitis and compared the testosterone levels under inflammation in the CMKLR1-/- and CCRL2-/- and WT mice.