Open AccessThe nuclear receptor steroidogenic factor 1 acts at multiple levels of the reproductive axis.
Author(s) -
Holly A. Ingraham,
Deepak S. Lala,
Yayoi Ikeda,
Xunrong Luo,
WenHui Shen,
Mark W. Nachtigal,
Rula Abbud,
John H. Nilson,
Keith L. Parker
Publication year - 1994
Publication title -
genes and development
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.136
H-Index - 438
eISSN - 1549-5477
pISSN - 0890-9369
DOI - 10.1101/gad.8.19.2302
Subject(s) - steroidogenic factor 1 , biology , endocrinology , medicine , nuclear receptor , orphan receptor , gonadotropic cell , in situ hybridization , anterior pituitary , gonadotropin releasing hormone receptor , gonadotropin , gonadotropin releasing hormone , hormone , pituitary gland , luteinizing hormone , gene expression , transcription factor , gene , genetics
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 (LH beta, FSH beta, and the receptor for gonadotropin-releasing hormone), whereas they exhibited decreased but detectable expression of the alpha-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 FSH beta and LH beta 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 alpha-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.