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Submitted on August 13, 2003
Accepted on September 15, 2003
and FSH
gene transcription by androgens: Testosterone directly stimulates FSH
transcription independent from its role on follistatin gene expression
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
-subunit mRNAs are differentially regulated by androgens. Testosterone (T) suppresses LH
and increases FSH
. We aimed to determine if androgens regulate LH
and FSH
transcription (as measured by changes in primary transcripts, PT) and to determine if androgens act directly on FSH
or via the intrapituitary activin/follistatin (FS) system. In castrate+GnRH antagonist treated rats, T increased FSH
PT between 3 h and 48 h. In contrast, T suppressed LH
PT. The increases in FSH
mRNA and PT were associated with reduced FS mRNA. Activin
B mRNA was modestly suppressed. The increase in FSH
PT after T was androgen specific. Both T and DHT increased FSH
PT 2-fold, and decreased both FS and
B mRNA. Estradiol suppressed FSH
PT 3-fold and had no effect on FS or
B mRNAs. LH
PT was suppressed by DHT. To determine if T stimulation of FSH
PT reflected a decrease in pituitary FS, we gave androgen in the presence of exogenous FS in vitro. T and DHT increased FSH
PT 2- to 3-fold. FS alone decreased FSH
PT 40%, but did not diminish the increase FSH
PT in response to T. Testosterone, DHT, and FS did not affect FS mRNA,
B mRNA, or LH
PT. In conclusion, androgens acting directly on the pituitary increase FSH
and decrease LH
transcription. The increase in FSH
PT in response to T was androgen specific, and occurs in the presence of excess FS, suggesting that T stimulates FSH
transcription independently of modulation of FS.
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