The nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis

Holly A. Ingraham, Deepak S. Lala, Yayoi Ikeda, Xunrong Luo, Wen Hui Shen, Mark W. Nachtigal, Rula Abbud, John H. Nilson, Keith L. Parker*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

486 Scopus citations

Abstract

Steroidogenic factor 1 (SF-1), an orphan nuclear receptor, regulates the enzymes that produce sex steroids, and disruption of the Ftz-F1 gene encoding SF-1 precludes adrenal and gonadal development. We now study the role of SF- 1 at other levels of the hypothalamic/pituitary/gonadal axis. In Ftz-F1- disrupted mice, immunohistochemical analyses with antibodies against pituitary trophic hormones showed a selective loss of gonadotrope-specific markers, supporting the role of SF-1 in gonadotrope function. In situ hybridization analyses confirmed these results; pituitaries from Ftz-F1- disrupted mice lacked transcripts for three gonadotrope-specific markers (LHβ, FSHβ, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the α-subunit of glycoprotein hormones. SF-1 transcripts in the developing mouse pituitary, which first became detectable at embryonic day 13.5-14.5, preceded the appearance of FSHβ and LHβ transcripts. In adult rat pituitary cells, SF-1 transcripts colocalized with immunoreactivity for the gonadotrope-specific LH. Finally, SF-1 interacted with a previously defined promoter element in the glycoprotein hormone α-subunit gene, providing a possible mechanism for the impaired gonadotropin expression in Ftz-F1-disrupted mice. These studies establish novel roles of this orphan nuclear receptor in reproductive function.

Original languageEnglish (US)
Pages (from-to)2302-2312
Number of pages11
JournalGenes and Development
Volume8
Issue number19
DOIs
StatePublished - Oct 1 1994

Keywords

  • Nuclear receptor SF-1
  • gonadal development
  • reproductive function

ASJC Scopus subject areas

  • Genetics
  • Developmental Biology

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