Abstract
Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, initially was isolated as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Thereafter, analyses of sites of SF-1 expression during mouse embryological development hinted at considerably expanded roles for SF-1, roles that were strikingly confirmed through the analyses of SF-1 knockout mice. These SF-1 knockout mice exhibited adrenal and gonadal agenesis, associated with male-to-female sex reversal of their internal and external genitalia and death from adrenocortical insufficiency. These findings showed unequivocally that SF-1 is essential for the embryonic survival of the primary steroidogenic organs, SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), establishing that SF-1 regulates reproductive function at all three levels of the hypothalamic-pituitary- gonadal axis. This article reviews the experiments that have defined these essential roles of SF-1 in endocrine development and highlights important areas for future studies.
Original language | English (US) |
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Pages (from-to) | 13-18 |
Number of pages | 6 |
Journal | Journal of Steroid Biochemistry and Molecular Biology |
Volume | 69 |
Issue number | 1-6 |
DOIs | |
State | Published - Apr 1999 |
Funding
We thank the many colleagues and collaborators who have contributed to the work reviewed here. Studies in our laboratory were supported by the Howard Hughes Medical Institute and the National Institutes of Health (HL 48460).
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism
- Biochemistry
- Molecular Medicine
- Molecular Biology
- Endocrinology
- Clinical Biochemistry
- Cell Biology