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This version published online on December 30, 2003
Molecular Endocrinology, doi:10.1210/me.2003-0115
Molecular Endocrinology Vol. 0, No. 2003 200301151-
doi:10.1210/me.2003-0115
Copyright © 2003 by the Endocrine Society.
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Submitted on April 2, 2003
Accepted on December 23, 2003

Androgen Regulates FSH{beta} Gene Expression in an Activin-Dependent Manner in Immortalized Gonadotropes

THOMAS J. SPADY1, RANA SHAYYA1, VARYKINA G. THACKRAY1, LISA EHRENSBERGER1, JANICE S. BAILEY1, and PAMELA L. MELLON1*

1 Departments of Reproductive Medicine and Neurosciences, Center for the Study of Reproductive Biology and Disease, University of California, San Diego, La Jolla, California 92093-0674

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

Little is known about the molecular mechanisms of androgen regulation of the FSH{beta} gene; however, studies suggest that it consists of a complex feedback loop that involves multiple mechanisms acting at both the level of the hypothalamus and the pituitary. In the present study, we address androgen regulation of the FSH{beta} gene in immortalized gonadotrope cells and investigate the roles of activin and GnRH (GnRH) in androgen action. Using transient transfection assays in the FSH{beta}-expressing mouse gonadotrope cell line, L{beta}T2, we demonstrate that androgens stimulate expression of an ovine FSH{beta} reporter gene in a dose-dependent manner. Mutation of either of two conserved androgen response elements at -245/-231 and -153/-139 within the proximal region of the ovine FSH{beta} gene promoter abolishes this stimulation and androgen receptor binds directly to the -244 ARE in vitro. Androgen induction of the FSH{beta} reporter gene is also dependent upon the activin autocrine loop present in the L{beta}T2 cells, as well as an activin-response element at -138/-124 of the FSH{beta} gene. However, activin regulation of other genes remains unaffected by androgens. In addition, androgens stimulate expression of a mouse GnRH receptor reporter gene, and thus may indirectly augment the response of the FSH{beta} gene to GnRH. Taken together, these data demonstrate that, in mouse gonadotropes, androgens act directly on the ovine FSH{beta} gene to stimulate expression by a mechanism that is dependent upon activin, as well as acting indirectly, potentially through a second mechanism that may be dependent upon induction of GnRH receptor.


Key words: testosterone • gonadotrope • follicle-stimulating hormone • GnRH receptor • activin

NURSA Molecule Pages Link:

Nuclear Receptors:   AR
Ligands:   Dihydrotestosterone



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