title: Steroidogenic factor 1: an essential mediator of endocrine development.
abstract: 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-I 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.
authors.affiliation: Department of Internal Medicine and Pharmacology, University of Texas Southwestern Medical Center, Dallas 75390, USA. keith.parker@email.swmed.edu
authors.forename: Keith L
authors.initials: KL
authors.lastname: Parker
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Rice
authors.forename: Deepak S
authors.initials: DS
authors.lastname: Lala
authors.forename: Yayoi
authors.initials: Y
authors.lastname: Ikeda
authors.forename: Xunrong
authors.initials: X
authors.lastname: Luo
authors.forename: Margaret
authors.initials: M
authors.lastname: Wong
authors.forename: Marit
authors.initials: M
authors.lastname: Bakke
authors.forename: Liping
authors.initials: L
authors.lastname: Zhao
authors.forename: Claudia
authors.initials: C
authors.lastname: Frigeri
authors.forename: Neil A
authors.initials: NA
authors.lastname: Hanley
authors.forename: Nancy
authors.initials: N
authors.lastname: Stallings
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Schimmer
mesh_terms: D000818:Animals; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D004702:Endocrine Glands / Q000196:embryology / Q000254:growth & development*; D051717:Fushi Tarazu Transcription Factors; D015870:Gene Expression; D005786:Gene Expression Regulation; D018398:Homeodomain Proteins; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation; D018160:Receptors, Cytoplasmic and Nuclear; D054339:Steroidogenic Factor 1; D014157:Transcription Factors / Q000172:deficiency / Q000235:genetics / Q000502:physiology*
chemical_list: 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