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This version published online on September 25, 2003
Endocrinology, doi:10.1210/en.2003-1047
A more recent version of this article appeared on January 1, 2004
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Submitted on August 13, 2003
Accepted on September 15, 2003

Regulation of LH{beta} and FSH{beta} gene transcription by androgens: Testosterone directly stimulates FSH{beta} transcription independent from its role on follistatin gene expression

Laura L. Burger1*, Daniel J. Haisenleder1, Kevin W. Aylor1, Alan C. Dalkin1, Kathleen A Prendergast1, and John C. Marshall1

1 Division of Endocrinology, Department of Internal Medicine, and the Center for Research in Reproduction. University of Virginia, Charlottesville, VA 22908.

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

The gonadotropin {beta}-subunit mRNAs are differentially regulated by androgens. Testosterone (T) suppresses LH{beta} and increases FSH{beta}. We aimed to determine if androgens regulate LH{beta} and FSH{beta} transcription (as measured by changes in primary transcripts, PT) and to determine if androgens act directly on FSH{beta} or via the intrapituitary activin/follistatin (FS) system. In castrate+GnRH antagonist treated rats, T increased FSH{beta} PT between 3 h and 48 h. In contrast, T suppressed LH{beta} PT. The increases in FSH{beta} mRNA and PT were associated with reduced FS mRNA. Activin {beta}B mRNA was modestly suppressed. The increase in FSH{beta} PT after T was androgen specific. Both T and DHT increased FSH{beta} PT 2-fold, and decreased both FS and {beta}B mRNA. Estradiol suppressed FSH{beta} PT 3-fold and had no effect on FS or {beta}B mRNAs. LH{beta} PT was suppressed by DHT. To determine if T stimulation of FSH{beta} PT reflected a decrease in pituitary FS, we gave androgen in the presence of exogenous FS in vitro. T and DHT increased FSH{beta} PT 2- to 3-fold. FS alone decreased FSH{beta} PT 40%, but did not diminish the increase FSH{beta} PT in response to T. Testosterone, DHT, and FS did not affect FS mRNA, {beta}B mRNA, or LH{beta} PT. In conclusion, androgens acting directly on the pituitary increase FSH{beta} and decrease LH{beta} transcription. The increase in FSH{beta} PT in response to T was androgen specific, and occurs in the presence of excess FS, suggesting that T stimulates FSH{beta} transcription independently of modulation of FS.


Key words: gonadotropin • testosterone • GnRH • follistatin • transcription




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