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This version published online on May 1, 2003
Molecular Endocrinology, doi:10.1210/me.2002-0286
A more recent version of this article appeared on August 1, 2003
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Submitted on August 19, 2002
Accepted on April 22, 2003

Nuclear Factor-Y and Steroidogenic Factor-1 Physically and Functionally Interact to Contribute to Cell-Specific Expression of the Mouse FSH{beta} Gene

Suzanne B.R. Jacobs1, Djurdjica Coss1, Shauna M. McGillivray1, and Pamela L. Mellon1*

1 Department of Reproductive Medicine, University of California, San Diego, La Jolla, California 92093-0674

* To whom correspondence should be addressed. E-mail: pmellon{at}ucsd.edu.

FSH (FSH) is a heterodimeric glycoprotein hormone secreted from the gonadotrope cell population of the anterior pituitary. Despite its crucial role in mammalian reproduction, very little is known about regulation of the FSH {beta}-subunit gene at the molecular level. In this report, we examine the basis for cell-specific expression of FSH{beta} using the mouse L{beta}T2 and {alpha}T3-1 gonadotrope-derived cell lines. Characterization of the hormonal content of L{beta}T2 and {alpha}T3-1 cells at the protein level classifies these cells as relatively mature and immature gonadotropes, respectively. We studied L{beta}T2 cell-specific expression of FSH{beta} using 398 base-pairs of the mouse FSH{beta} regulatory region linked to a luciferase reporter gene in transient transfection assays. This mouse FSH{beta} promoter can direct reporter gene expression specifically to L{beta}T2 cells when compared with other pituitary and nonpituitary-derived cell lines, including {alpha}T3-1 cells. Furthermore, it is induced by activin and interruption of the autocrine activin loop in L{beta}T2 cells by the addition of follistatin reduces its expression. Truncation analysis indicates that several regions of the promoter are involved in this specificity and that these can be dissociated from activin regulation. We identify binding sites for the orphan nuclear receptor steroidogenic factor-1 (SF-1) and the heterotrimeric transcription factor nuclear factor-Y (NF-Y) and show that these elements functionally interact to regulate FSH{beta} gene expression in an L{beta}T2 cell-specific manner. Moreover, SF-1 and NF-Y are shown to physically interact with each other. This study is the first to demonstrate the presence of basal FSH{beta} protein in L{beta}T2 cells and to identify specific elements within the FSH{beta} promoter that contribute to basal and cell-specific expression of the gene.


Key words: FSH • steroidogenic factor 1 • nuclear factor-Y • pituitary gonadotrope

NURSA Molecule Pages Link:

Nuclear Receptors:   SF-1



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