Central nervous system-specific knockout of steroidogenic factor 1 results in increased anxiety-like behavior

Liping Zhao, Woo Kim Ki, Yayoi Ikeda, Kimberly K. Anderson, Laurel Beck, Stephanie Chase, Stuart A. Tobet, Keith L. Parker

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Steroidogenic factor 1 (SF-1) plays key roles in adrenal and gonadal development, expression of pituitary gonadotropins, and development of the ventromedial hypothalamic nucleus (VMH). If kept alive by adrenal transplants, global knockout (KO) mice lacking SF-1 exhibit delayed-onset obesity and decreased locomotor activity. To define specific roles of SF-1 in the VMH, we used the Cre-loxP system to inactivate SF-1 in a central nervous system (CNS)-specific manner. These mice largely recapitulated the VMH structural defect seen in mice lacking SF-1 in all tissues. In multiple behavioral tests, mice with CNS-specific KO of SF-1 had significantly more anxiety-like behavior than wild-type littermates. The CNS-specific SF-1 KO mice had diminished expression or altered distribution in the mediobasal hypothalamus of several genes whose expression has been linked to stress and anxiety-like behavior, including brain-derived neurotrophic factor, the type 2 receptor for CRH (Crhr2), and Ucn 3. Moreover, transfection and EMSAs support a direct role of SF-1 in Crhr2 regulation. These findings reveal important roles of SF-1 in the hypothalamic expression of key regulators of anxiety-like behavior, providing a plausible molecular basis for the behavioral effect of CNS-specific KO of this nuclear receptor.

Original languageEnglish
Pages (from-to)1403-1415
Number of pages13
JournalMolecular Endocrinology
Volume22
Issue number6
DOIs
Publication statusPublished - 2008 Jun 1

    Fingerprint

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Endocrinology

Cite this