García-López Angel, Bogerd Jan, Granneman Joke C M, van Dijk Wytske, Trant John M, Taranger Geir Lasse, Schulz Rüdiger W
Division Endocrinology and Metabolism, Department of Biology, Faculty of Sciences, Utrecht University, CH Utrecht, The Netherlands.
Endocrinology. 2009 Jan;150(1):357-65. doi: 10.1210/en.2008-0447. Epub 2008 Aug 28.
This report aimed to establish, using African catfish, Clarias gariepinus, as model species, a basis for understanding a well-known, although not yet clarified, feature of male fish reproductive physiology: the strong steroidogenic activity of FSHs. Assays with gonadotropin receptor-expressing cell lines showed that FSH activated its cognate receptor (FSHR) with an at least 1000-fold lower EC50 than when challenging the LH receptor (LHR), whereas LH stimulated both receptors with similar EC50s. In androgen release bioassays, FSH elicited a significant response at lower concentrations than those required to cross-activate of the LHR, indicating that FSH stimulated steroid release via FSHR-dependent mechanisms. LHR/FSHR-mediated stimulation of androgen release was completely abolished by H-89, a specific protein kinase A inhibitor, pointing to the cAMP/protein kinase A pathway as the main route for both LH- and FSH-stimulated steroid release. Localization studies showed that intratubular Sertoli cells express FSHR mRNA, whereas, as reported for the first time in a vertebrate, catfish Leydig cells express both LHR and FSHR mRNA. Testicular FSHR and LHR mRNA expression increased gradually during pubertal development. FSHR, but not LHR, transcript levels continued to rise between completion of the first wave of spermatogenesis at about 7 months and full maturity at about 12 months of age, which was associated with a previously recorded approximately 3-fold increase in the steroid production capacity per unit testis weight. Taken together, our data strongly suggest that the steroidogenic potency of FSH can be explained by its direct trophic action on FSHR-expressing Leydig cells.
本报告旨在以非洲鲶鱼(Clarias gariepinus)为模式物种,为理解雄鱼生殖生理学中一个众所周知但尚未阐明的特征——促卵泡激素(FSHs)强大的类固醇生成活性——奠定基础。对表达促性腺激素受体的细胞系进行的检测表明,与刺激促黄体生成素受体(LHR)相比,FSH激活其同源受体(FSHR)时的半数有效浓度(EC50)至少低1000倍,而LH以相似的EC50刺激这两种受体。在雄激素释放生物测定中,FSH在比交叉激活LHR所需浓度更低时就能引发显著反应,表明FSH通过FSHR依赖性机制刺激类固醇释放。H - 89(一种特异性蛋白激酶A抑制剂)完全消除了LHR/FSHR介导的雄激素释放刺激,这表明环磷酸腺苷/蛋白激酶A途径是LH和FSH刺激类固醇释放的主要途径。定位研究表明,管内支持细胞表达FSHR mRNA,而正如在脊椎动物中首次报道的那样,鲶鱼的睾丸间质细胞同时表达LHR和FSHR mRNA。在青春期发育过程中,睾丸FSHR和LHR mRNA表达逐渐增加。在大约7个月时第一波精子发生完成到大约12个月完全成熟之间,FSHR而非LHR的转录水平持续上升,这与之前记录的单位睾丸重量类固醇生成能力约3倍增加有关。综上所述,我们的数据强烈表明,FSH的类固醇生成效力可通过其对表达FSHR的睾丸间质细胞的直接营养作用来解释。