Heckert Leslie L, Griswold Michael D
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City 66160, USA.
Recent Prog Horm Res. 2002;57:129-48. doi: 10.1210/rp.57.1.129.
Results from experiments using mouse models suggest that the role of follicle-stimulating hormone (FSH) in spermatogenesis is the regulation of Sertoli cell proliferation and, ultimately, the size and spermatogenic capacity of the testis. The regulation of the expression of the FSH receptor (FSHR) gene is very cell specific and plays an initial role in the ultimate response of the Sertoli cells to FSH. The extreme cell specificity and the importance of the FSH response to spermatogenesis have led to an extensive characterization of the promoter of the FSHR gene. Several widely expressed transcription factors - including USF 1 and 2, GATA-1, and SF-1 and potential elements such as an E2F site and an Inr region - have been shown to contribute to the maximal transcription of the transfected FSHR gene. However, these experiments have failed to provide clues as to the cell-specific expression of the FSHR gene. In both cell transfections and in transgenic mice, the promoter can direct expression of transgenes promiscuously. The rodent FSHR promoter contains conserved CpG dinucleotides that were shown to be methylated in nonexpressing cells and tissue but unmethylated in Sertoli cells. The methylated CpG sites could interfere with the binding of general transcription factors and/or lead to a repressive chromatin structure in the nonexpressing cells. While yet-undiscovered cell-specific factors may play a role in the expression of the FSHR gene, repression and activation of local chromatin structure are likely to be involved.
使用小鼠模型的实验结果表明,促卵泡激素(FSH)在精子发生中的作用是调节支持细胞的增殖,并最终调节睾丸的大小和生精能力。FSH受体(FSHR)基因表达的调节具有很强的细胞特异性,并在支持细胞对FSH的最终反应中起初始作用。FSH反应对精子发生的极端细胞特异性和重要性导致了对FSHR基因启动子的广泛表征。几种广泛表达的转录因子——包括USF 1和2、GATA-1以及SF-1,以及诸如E2F位点和Inr区域等潜在元件——已被证明有助于转染的FSHR基因的最大转录。然而,这些实验未能提供有关FSHR基因细胞特异性表达的线索。在细胞转染和转基因小鼠中,启动子都可以随意指导转基因的表达。啮齿动物FSHR启动子包含保守的CpG二核苷酸,已证明在非表达细胞和组织中这些二核苷酸被甲基化,而在支持细胞中未被甲基化。甲基化的CpG位点可能会干扰一般转录因子的结合和/或导致非表达细胞中形成抑制性染色质结构。虽然尚未发现的细胞特异性因子可能在FSHR基因的表达中起作用,但局部染色质结构的抑制和激活可能也参与其中。