Tissue-specific knockouts of steroidogenic factor 1

Liping Zhao, Marit Bakke, Neil A. Hanley, Gregor Majdic, Nancy R. Stallings, Pancharatnam Jeyasuria, Keith L. Parker

Research output: Contribution to journalArticle

47 Scopus citations

Abstract

Targeted gene disruption has produced knockout (KO) mice globally deficient in the orphan nuclear receptor steroidogenic factor 1 (SF-1). These SF-1 KO mice lacked adrenal glands and gonads, and also had impaired expression of gonadotropins in pituitary gonadotropes and marked structural abnormalities of the ventromedial hypothalamic nucleus (VMH). To define the roles of SF-1 within discrete sites of the hypothalamic-pituitary-steroidogenic organ axis, we have sought to make tissue-specific SF-1 KO mice (as reviewed here). We first used adrenal transplants to restore adrenal function in global SF-1 KO mice, providing a physiological form of a "VMH-specific" KO to study the roles of SF-1 in weight regulation. These adrenal-transplanted SF-1 KO mice became obese due to decreased locomotor activity, providing a novel model of hypothalamic obesity. Mice with a pituitary-specific KO of SF-1 mediated by the Cre-loxP recombination strategy exhibited hypogonadotropic hypogonadism, revealing essential roles of SF-1 in pituitary function in vivo. Ongoing studies seek to inactivate SF-1 in the brain or specific gonadal cell types, thereby defining its roles in development and function at these sites. In addition, we review our use of bacterial artificial chromosome transgenesis to develop a fluorescent marker for cells that express SF-1.

Original languageEnglish (US)
Pages (from-to)89-94
Number of pages6
JournalMolecular and Cellular Endocrinology
Volume215
Issue number1-2
DOIs
StatePublished - Feb 27 2004

Keywords

  • Cre recombinase
  • Green fluorescent protein
  • Steroidogenesis
  • Tissue-specific knockouts

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Endocrinology

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  • Cite this

    Zhao, L., Bakke, M., Hanley, N. A., Majdic, G., Stallings, N. R., Jeyasuria, P., & Parker, K. L. (2004). Tissue-specific knockouts of steroidogenic factor 1. Molecular and Cellular Endocrinology, 215(1-2), 89-94. https://doi.org/10.1016/j.mce.2003.11.009