INTRATESTICULAR REGULATION OF INHIBIN AND POMC GENES

在目前的资助期间，我们和其他人证明， 睾丸POMC基因不仅在睾丸间质细胞中表达， 生殖细胞 该基因的表达依赖于 这两种细胞类型之间的联系。 近年来，对阿糖胞苷的研究 研究生殖生理调节的新领域。 由支持细胞合成的抑制素肽显示出调节 睾丸间质细胞类固醇生成除了其众所周知的功能外， 调节垂体FSH分泌。 因此，也可以认为， 是精子发生的重要调节器。 此外，POMC衍生的 肽是支持细胞功能的重要旁分泌调节剂， 生产。 这些新的观察结果表明， 睾丸支持细胞中POMC基因的表达 和生殖细胞可以相互调节。 因此我们建议 以睾丸素和POMC为模型系统，研究睾丸内 支持细胞、间质细胞和生殖细胞中基因表达的调节。 的 POMC基因的结构及其在肿瘤细胞中的调控 睾丸在过去的几年里一直在积累。 但 Sertoli细胞中Serbin基因的表达及其调控 还没有得到很好的研究。 我们的第一个具体目标是描述 大鼠睾丸中编码β-D-半胱氨酸亚基的mRNA的结构。 其次，我们将研究在体外的差异调节， 体外培养大鼠睾丸支持细胞中BMP 1亚基基因的表达 已知影响支持细胞功能的因素，通过旁分泌调节剂 （POMC-衍生肽和Leydig细胞蛋白），或通过细胞内 交互. 我们将进一步研究上述调节剂是否 影响基因转录或mRNA稳定性。 使用此 然后，我们将研究睾丸内调节的信息， Leydig影响下的动物系统中的拟南芥素基因表达 和/或生殖细胞功能或POMC基因调节，受 垂体激素、雄激素或生殖细胞的不同阶段 （具体目标A.3）。 最后，我们将鉴定调控DNA元件， 启动子/调节区和启动子应答元件， 负责Escherichin α-亚基基因转录， 确定参与组织特异性 大鼠睾丸中POMC基因转录的改变（具体目标A.4）。 我们从这些研究所得的资料，将有助我们 了解男性生殖的性腺内控制。

During the present funding period, we and others demonstrated that testicular POMC gene is expressed not only in Leydig cells but also in germ cells. the expression of this gene depends upon the interaction between these two cell types. The recent studies on inhibin have opened a new field for studying the regulation of reproductive physiology. Inhibin peptides synthesized by Sertoli cells were shown to modulate Leydig cell steroidogenesis in addition to their well-know function of regulating pituitary FSH secretion. Thus, inhibin is also considered to be an important regulator of spermatogenesis. In addition, POMC-derived peptides are important paracrine modulators of Sertoli cell function and inhibin production. These new observations suggest that the expression of inhibin genes in Sertoli cells and the expression POMC gene in Leydig and germ cells may be regulated by each other. We therefore propose to use inhibin and POMC as model systems to study the intratesticular regulation of gene expression in Sertoli, Leydig, and germ cells. The information on the structure of POMC gene and its regulation in the testis have been accumulated in the past years. However, the expressions of inhibin genes and their regulations in the Sertoli cells have not been well studied. Our first specific aim is to characterize the structure of mRNAs coding for inhibin subunits in rat testis. Secondly, we will investigate the in vitro differential regulation of inhibin subunit gene expression in rat Sertoli cell primary cultures by factors know to affect Sertoli cell functions, by paracrine regulators (POMC-derived peptides and Leydig cell proteins), or by cellular interactions. We will further investigate whether the above modulators affect the gene transcription or the mRNA stability. Using this information we will then investigate the intratesticular regulation of inhibin gene expression in animal systems under the influence of Leydig and/or germ cell functions or of POMC gene modulation, affected by pituitary hormones, androgens, or different stages of germ cells (Specific Aim A.3). finally, we will identify regulatory DNA elements, the promotor/regulatory regions and hormone-responsive elements, that are responsible for inhibin alpha-subunit gene transcription, and determine the molecular mechanism involved in the tissue-specific altered transcription of POMC gene in rat testis (Specific Aim A.4). The information we will obtain from these studies will facilitate our understanding of the intragonadal control of male reproduction.