Salehi Sajad, Adeshina Ikeoluwa, Chen Haolin, Zirkin Barry R, Hussain Mehboob A, Wondisford Fredric, Wolfe Andrew, Radovick Sally
Divisions of Endocrinology (S.S., I.A., A.W., S.R.) and Metabolism (B.A.H., F.W.), Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Department of Biochemistry and Molecular Biology (H.C., B.R.Z.), Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland 21205.
Endocrinology. 2015 Apr;156(4):1514-22. doi: 10.1210/en.2014-1606. Epub 2015 Jan 30.
Kisspeptin, encoded by the Kiss1 gene, binds to a specific G protein-coupled receptor (kisspeptin1 receptor) to regulate the central reproductive axis. Kisspeptin has also been reported to be expressed in peripheral tissues, including the testes. However, factors regulating testicular kisspeptin and its role in reproduction are unknown. Our objective herein was to begin to address kisspeptin function in the testis. In particular, we sought to determine the level of kisspeptin in the testis in comparison with the brain and other tissues, how these levels change from the prepubertal period through sexual maturation, and the factors involved in kisspeptin regulation in the testis. Immunohistochemical analysis of testis sections using a validated kisspeptin antibody localized kisspeptin to the Leydig cells. Kisspeptin was not detected in germ cells or Sertoli cells within the seminiferous tubules at any developmental time period studied, from prepuberty to sexual maturation. A developmental time course of testicular kisspeptin revealed that its mRNA and protein levels increased during development, reaching robust levels at postnatal day 28, correlating with pubertal onset. In vitro studies of primary mouse Leydig cells, as well as in vivo studies, indicated clearly that LH is involved in regulating levels of Leydig cell kisspeptin. Interestingly, gonadectomy resulted in elevated LH but reduced serum kisspeptin levels, suggesting that testicular kisspeptin may be secreted. These data document kisspeptin expression in mouse Leydig cells, its secretion into peripheral serum, and its regulation by changes in reproductive neuroendocrine function.
由Kiss1基因编码的亲吻素与特定的G蛋白偶联受体（亲吻素1受体）结合，以调节中枢生殖轴。据报道，亲吻素也在外周组织中表达，包括睾丸。然而，调节睾丸亲吻素的因素及其在生殖中的作用尚不清楚。我们在此的目的是开始研究亲吻素在睾丸中的功能。具体而言，我们试图确定睾丸中亲吻素的水平，并与大脑和其他组织进行比较，研究从青春期前到性成熟期间这些水平如何变化，以及睾丸中亲吻素调节所涉及的因素。使用经过验证的亲吻素抗体对睾丸切片进行免疫组织化学分析，结果显示亲吻素定位于睾丸间质细胞。在研究的任何发育时期，从青春期前到性成熟，在生精小管内的生殖细胞或支持细胞中均未检测到亲吻素。睾丸亲吻素的发育时间进程显示，其mRNA和蛋白质水平在发育过程中升高，在出生后第28天达到较高水平，这与青春期开始相关。对原代小鼠睾丸间质细胞的体外研究以及体内研究均清楚表明，促黄体生成素（LH）参与调节睾丸间质细胞亲吻素水平。有趣的是，去势导致LH升高，但血清亲吻素水平降低，这表明睾丸亲吻素可能会分泌。这些数据证明了亲吻素在小鼠睾丸间质细胞中的表达、其分泌到外周血清中以及其受生殖神经内分泌功能变化的调节。
