Steroidogenic factor-1 as a therapeutic target for of severe ovarian failure

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Aromatization of androgens, catalyzed by aromatase P450, is essential for estrogen biosynthesis, hetero for folliculogenesis. Here we investigated the transcriptional regulation of aromatase in granulosa cells and identify both steroidogenic factor-1 and LRH-1 as important regulatory factors binding to the nuclear half site of proximal promoter PII of aromatase. Both transcriptional factors were expressed in granulosa cell of healthy growing follicles and luteal cells. COV432, a cell lines established from a human granulosa cell, express exclusively LRH-1 and granulosa cells in growing follicle expressed much LRH-1 than SF-l. Granulosa luteal cells expressed much LRH-1, while theca luteal cells almost exclusively expressed SF-1. Co-expression of SF-1 or LRH-1 stimulated the expression of promoter vectors containing various lengths of PII sequences. We also investigated mechanism of IL-lb- and GnRH agonsit- induced induction of aromatase in endometriosis-derived stromal cells. IL-lb increased aromatase expression through COX2-dependent and COX2-independent mechanisms. GnRH agonists transiently stimulated aromatase expression through the activation of PKC. IGF-1 and BMP also stimulated aromatase expression in the presence of FSH.