Steroidogenic factor 1 (SF-1) is essential for ovarian development and function.
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.
Hanley
N A
NA
Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, TX 75235-8857, USA.
Ikeda
Y
Y
Luo
X
X
Parker
K L
KL
D000818:Animals; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D012734:Disorders of Sex Development; D005314:Embryonic and Fetal Development; D005260:Female; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000196:embryology / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010053:Ovary / Q000196:embryology* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000196:embryology / Q000378:metabolism; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D004268:DNA-Binding Proteins; D051717:Fushi Tarazu Transcription Factors; D018398:Homeodomain Proteins; C515057:NR5A1 protein, human; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors; C515058:steroidogenic factor 1, mouse