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CNS-specific ablation of steroidogenic factor 1 results in impaired female reproductive function.

Authors
  • Kim, Ki Woo1
  • Li, Shen
  • Zhao, Hongyu
  • Peng, Boya
  • Tobet, Stuart A
  • Elmquist, Joel K
  • Parker, Keith L
  • Zhao, Liping
  • 1 Division of Hypothalamic Research, Departments of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas 75390, USA.
Type
Published Article
Journal
Molecular Endocrinology
Publisher
The Endocrine Society
Publication Date
June 2010
Volume
24
Issue
6
Pages
1240–1250
Identifiers
DOI: 10.1210/me.2009-0206
PMID: 20339005
Source
Medline
License
Unknown

Abstract

The ventromedial hypothalamic nucleus (VMH) regulates a variety of homeostatic processes including female sexual behavior and reproduction. In the current study, we assessed the roles of steroidogenic factor 1 (SF-1) on reproductive function in the VMH using central nervous system-specific SF-1 knockout (SF-1 KO(nCre;F/-)) mice. Here we show that SF-1 KO(nCre;F/-) females exhibited marked impairment in female reproduction. Although male mice appeared to be normal in all aspects studied, including sexual behavior, SF-1 KO(nCre;F/-) females showed infertility or subfertility. Although adult SF-1 KO(nCre;F/-) females showed decreased or lacked corpora lutea, exogenous administration of gonadotropins induced the formation of multiple corpora lutea and induced normal ovulation, demonstrating that the ovaries are functionally intact. In addition, SF-1 KO(nCre;F/-) females stimulated with a synthetic GnRH agonist after priming exhibited markedly reduced LH secretion compared with wild-type littermates, arguing that disorganization in and around the VMH caused by SF-1 ablation interferes with the GnRH priming process or gonadotrope LH capacity. Furthermore, the SF-1 KO(nCre;F/-) females primed with estrogen benzoate and progesterone failed to induce steroid receptors around the VMH, consistent with impaired lordosis behavior in the SF-1 KO(nCre;F/-) females. Collectively, our results highlight that SF-1 in the VMH plays crucial roles in regulation of female reproductive function, presumably by organizing a precise neuronal connection and communication in and around the VMH.

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