期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2003
卷号：100
期号：16
页码：9348-9353
DOI：10.1073/pnas.1633592100
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：In addition to its role in causing Mullerian duct regression, Mullerian inhibiting substance (MIS) is implicated in the regulation of steroidogenesis, breast and prostate growth, and ovarian follicle recruitment, all of which are processes controlled or influenced by the hypothalamic-pituitary-gonadal axis. Whereas the direct effect of MIS on gonadal, prostate, and breast cells is under investigation, the ability of MIS to modulate pituitary function, thereby affecting those tissues indirectly, has not yet been studied. Using L{beta}T2 cells, a murine gonadotrope-derived cell line, we have evaluated the effects of MIS on the expression of the gonadotropin genes. We show that both L{beta}T2 cells and adult rat pituitaries express MIS type II receptor (MISRII) mRNA. Within 2 h, follicle-stimulating hormone {beta} subunit (FSH{beta}) mRNA levels are significantly induced by addition of MIS to L{beta}T2 cells and remain elevated through 8 h of treatment. Transcriptional activation of both the FSH{beta} and luteinizing hormone {beta} subunit (LH{beta}) gene promoters was observed by MIS, which enhances the effect of gonadotropin-releasing hormone (GnRH) agonist on the FSH{beta} gene promoter and synergizes with the GnRH agonist to stimulate LH{beta} gene promoter activity. Addition of MIS to L{beta}T2 cells stimulates the activity of the rat LH{beta} gene promoter with as little as 1 {micro}g/ml and in a dose-dependent manner. These studies report both MISRII expression in rat pituitary cells and a gonadotrope-derived cell line and MIS-mediated activation of LH{beta} and FSH{beta} gene expression, and suggest that MIS may modulate the hypothalamic-pituitary-gonadal axis at more than one level.
