Laboratory for Reproductive Health, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China Palo Alto Institute for Research and Education, Veterans Affairs Palo Alto Health Care System, Palo Alto, California 94304, USA Guangdong Key Laboratory of Nanomedicine, Guangdong, China.
J Endocrinol. 2014 Jan 8;220(2):155-63. doi: 10.1530/JOE-13-0275. Print 2014 Feb.
The novel adipokine chemerin plays a role in the regulation of lipid and carbohydrate metabolism, and recent reports of elevated chemerin levels in polycystic ovarian syndrome and preeclampsia have pointed to an emerging role of chemerin in reproduction. We hypothesised that chemerin, like other adipokines, may function to regulate male gonadal steroidogenesis. In this study, we show that chemerin and its three receptors chemokine-like receptor 1 (CMKLR1), G-protein-coupled receptor 1 (GPR1) and chemokine (C-C motif) receptor-like 2 were expressed in male reproductive tracts, liver and white adipose tissue. CMKLR1 and GPR1 proteins were localised specifically in the Leydig cells of human and rat testes by immunohistochemistry. The expression of chemerin and its receptors in rat testes was developmentally regulated and highly expressed in Leydig cells. In vitro treatment with chemerin suppressed the human chorionic gonadotropin (hCG)-induced testosterone production from primary Leydig cells, which was accompanied by the inhibition of 3β-hydroxysteroid dehydrogenase gene and protein expression. The hCG-activated p44/42 MAPK (Erk1/2) pathway in Leydig cells was also inhibited by chemerin cotreatment. Together, these data suggest that chemerin is a novel regulator of male gonadal steroidogenesis.
新型脂肪因子趋化素在脂质和碳水化合物代谢的调节中发挥作用,最近有报道称多囊卵巢综合征和先兆子痫患者的趋化素水平升高,这表明趋化素在生殖方面的作用正在显现。我们假设,趋化素与其他脂肪因子一样,可能在调节男性性腺甾体生成中发挥作用。在这项研究中,我们发现趋化素及其三个受体趋化因子样受体 1(CMKLR1)、G 蛋白偶联受体 1(GPR1)和趋化因子(C-C 基序)受体样 2 在男性生殖道、肝脏和白色脂肪组织中表达。免疫组织化学显示,CMKLR1 和 GPR1 蛋白特异性定位于人睾丸和大鼠睾丸的间质细胞中。趋化素及其受体在大鼠睾丸中的表达受发育调控,并在间质细胞中高度表达。趋化素体外处理可抑制人绒毛膜促性腺激素(hCG)诱导的原代间质细胞睾酮生成,同时伴有 3β-羟甾脱氢酶基因和蛋白表达的抑制。趋化素共处理还抑制了 hCG 激活的间质细胞中的 p44/42 MAPK(Erk1/2)通路。综上所述,这些数据表明趋化素是一种新型的男性性腺甾体生成调节剂。