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Steroidogenic factor 1 (SF-1) is essential for ovarian development and function
1Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75235-8857, USA.
Abstract:
The orphan nuclear receptor steroidogenic factor 1 (SF-1) was identified originally as a key regulator of the tissue-specific expression of the cytochrome P450 steroid hydroxylases. Hints at considerably broader roles for SF-1 came from analyses of its expression pattern in mouse embryos. As anticipated, SF-1 was expressed in the adrenal glands and gonads from their early stages of development. Surprisingly, SF-1 also was expressed outside of the primary steroidogenic tissues in the anterior pituitary and hypothalamus. SF-1 knockout mice dramatically confirmed its multiple essential roles in vivo. These mice lacked adrenal glands and gonads, leading to adrenocortical insufficiency and male-to-female sex reversal of their internal and external genitalia. SF-1 knockout mice also had impaired pituitary expression of gonadotropins and agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles of SF-1 at all three levels of the hypothalamic-pituitary-gonadal axis. With some focus on the ovary, this review summarizes experiments that have defined essential roles of SF-1 in endocrine development, and highlights important areas for future studies.
Insights
Steroidogenic factor 1 (SF-1) is crucial for adrenal and gonad development. SF-1 also regulates the hypothalamic-pituitary-gonadal axis, impacting pituitary and brain development.
Area of Science:
- Endocrinology
- Developmental Biology
- Molecular Biology
Background:
- Steroidogenic factor 1 (SF-1) is an orphan nuclear receptor.
- SF-1 regulates tissue-specific expression of cytochrome P450 steroid hydroxylases.
- SF-1 expression extends beyond steroidogenic tissues to the anterior pituitary and hypothalamus.
Purpose of the Study:
- To review the essential roles of SF-1 in endocrine development.
- To highlight future research directions for SF-1 studies, with a focus on the ovary.
Main Methods:
- Analysis of SF-1 expression patterns in mouse embryos.
- Phenotypic analysis of SF-1 knockout mice.
Main Results:
- SF-1 knockout mice lack adrenal glands and gonads, exhibiting adrenocortical insufficiency.
- SF-1 knockout mice display male-to-female sex reversal and impaired pituitary gonadotropin expression.
- SF-1 knockout mice show agenesis of the ventromedial hypothalamic nucleus (VMH), confirming roles across the HPG axis.
Conclusions:
- SF-1 plays essential, multifaceted roles in the development and function of the adrenal glands, gonads, pituitary, and hypothalamus.
- SF-1 is a critical regulator of the entire hypothalamic-pituitary-gonadal axis.
- Further research on SF-1, particularly concerning ovarian function, is warranted.