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STEROIDOGENIC FACTOR 1 (SF-1): MORE THAN JUST STEROIDOGENESIS.
Parker, Keith1, Zhao, Liping, Bakke, Marit, 1
ABSTRACT- The orphan nuclear receptor SF-1 was isolated initially as a critical regulator of the cytochrome P450 steroid hydroxylases. Subsequently, analyses of SF-1 knockout mice established additional essential roles in endocrine development and function. For example, SF-1 regulates the expression of anti-mullerian hormone in Sertoli cells, contributes to the expression of multiple genes that modulate reproduction in pituitary gonadotropes, and is essential for the development of the ventromedial hypothalamic nucleus. This complex phenotype has hindered efforts to delineate primary versus secondary effects of the SF-1 knockout. Ongoing experiments seek to inactivateSF-1 in a tissue-specific fashion. Using the common alpha subunit of glycoprotein hormone to target expression of the bacteriophage Cre recombinase, we demonstrated essential roles of SF-1 in gonadotropes, producing a novel genetic model of hypogonadotropic hypogonadism. Efforts are now underway to target Cre expression to the Sertoli/granulosa and Leydig/theca lineages, as well as to make VMH-specific SF-1 knockout mice. These studies will hopefully provide novel insights into how SF-1 plays its key roles in reproduction.
KEY WORDS: steroidogenic factor 1, gonadotropes, hypogonadotropic hypogonadism, infertilty
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