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Recent Progress in Hormone Research 57:19-36 (2002)
© 2002 The Endocrine Society

Steroidogenic Factor 1: an Essential Mediator of Endocrine Development

Keith L. Parker*, Douglas A. Rice*, Deepak S. Lala*, Yayoi Ikeda*, Xunrong Luo*, Margaret Wong*, Marit Bakke*, Liping Zhao*, Claudia Frigeri{dagger}, Neil A. Hanley*, Nancy Stallings* and Bernard P. Schimmer{dagger}

* Departments of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas 75390
{dagger} Banting and Best Department of Medical Research, University of Toronto, Toronto M5G 1L6 Canada

The orphan nuclear receptor steroidogenic factor 1 (SF-1, also called Ad4BP and officially designated NR5A1) has emerged as an essential regulator of endocrine development and function. Initially identified as a tissue-specific transcriptional regulator of the cytochrome P450 steroid hydroxylases, SF-1 has considerably broader roles, as evidenced from studies in knockout mice lacking SF-1. The SF-1-knockout mice lacked adrenal glands and gonads and therefore died from adrenal insufficiency within the first week after birth. In addition, SF-1 knockout mice exhibited male-to-female sex reversal of their internal and external genitalia, impaired expression of multiple markers of pituitary gonadotropes, and agenesis of the ventromedial hypothalamic nucleus (VMH). These studies delineated essential roles of SF-1 in regulating endocrine differentiation and function at multiple levels, particularly with respect to reproduction. This chapter will review the experiments that established SF-1 as a pivotal, global determinant of endocrine differentiation and function. We next discuss recent insights into the mechanisms controlling the expression and function of SF-1 as well as the current status of research aimed at delineating its roles in specific tissues. Finally, we highlight areas where additional studies are needed to expand our understanding of SF-1 action.




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