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BOR - Papers in Press, published online ahead of print October 15, 2003.
Biol Reprod 2003, 10.1095/biolreprod.103.021733
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Submitted August 14, 2003
Returned for revision September 10, 2003
Accepted October 8, 2003

Pitutitary


Pituitary Follistatin Gene Expression in Female Rats: Evidence That Inhibin Regulates Transcription

Kathleen A. Prendergast *, Laura L. Burger , Kevin W. Aylor , Daniel J. Haisenleder , Alan C. Dalkin , and John C. Marshall

* To whom correspondence should be addressed. E-mail: kap2k{at}virginia.edu.

Abstract
Follistatin (FS), along with the members of the TGF{beta} family activin and inhibin, are important regulators of FSH secretion and messenger RNA production. While activin and inhibin appear to function as tonic modulators of FSH (stimulatory and inhibitory, respectively), dynamic changes in FS are noted through the estrous cycle and under varying physiological experimental paradigms. This suggests that FS is a major contributor to the precisely coordinated secretion of FSH that maintains reproductive function. The aim of this study was to investigate changes in FS, in particular the early (<12h) rise observed after ovariectomy, and to determine whether these changes were as a consequence of variations in gene transcription rates. FS primary transcript (PT) and mRNA was found to increase 3-fold 12h post-OVX, indicating increased gene transcription during this time period. Replacement with estradiol (E2) and/or blockade of GnRH had only modest effects on FS PT concentration. Inhibin immunoneutralization of intact rats resulted in a 3-fold increase in FS PT 12h after administration of inhibin-{alpha} antisera. Significant increases in FS mRNA at both 2 and 12 hours also suggested that inhibin also may have effects on message stability. After administration of rh inhibin A, there was a prompt decline in both FS PT and mRNA. These results indicate that inhibin is a major regulator of FS, both by transcriptional and non-transcriptional mechanisms.

Key words: Follicle-stimulating hormone • Follistatin • Gene regulation • Gonadotropin-releasing hormone • Inhibin


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