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BOR - Papers in Press, published online ahead of print May 31, 2006.
Biol Reprod 2006, 10.1095/biolreprod.106.053017
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biolreprod.106.053017v1
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BIOLOGY OF REPRODUCTION 75, 360–369 (2006)
DOI: 10.1095/biolreprod.106.053017
© 2006 by the Society for the Study of Reproduction, Inc.


Research Article

Regulation of Aryl Hydrocarbon Receptor Expression in Rat Granulosa Cells1

Ursula A. Bussmann 3, and J. Lino Barañao 2 34 

Instituto de Biología y Medicina Experimental-CONICET3 Facultad de Ciencias Exactas y Naturales,4 Universidad de Buenos Aires, Buenos Aires 1428, Argentina

ABSTRACT

The aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor that mediates most of the toxic and endocrine-disruptive actions of aromatic compounds in the ovary. Paradoxically, this receptor has been shown to play important roles in normal female reproductive function as well. Although knowledge of AHR expression regulation in the ovary is of crucial significance to understand the receptor biology and its function in reproductive physiology, there are only limited data in this area. The purpose of the present study was to establish the possible regulation that AHR might undergo in ovarian cells. Here we show that the hormones FSH and estradiol are able to reduce AHR protein and transcript levels in granulosa cells in a way that parallels the changes observed in ovarian tissue across the rat estrous cycle. These findings suggest that estradiol and FSH would be cycle-associated endogenous modulators of AHR expression. In addition, we show that in granulosa cells the receptor is rapidly downregulated via proteasomal degradation following treatment with AHR ligands. However, prolonged treatment with an agonist caused an increase in Ahr mRNA levels. These actions would constitute a regulatory mechanism that both attenuates AHR signal rapidly and replenishes the cellular receptor pool in the long term. In conclusion, our results indicate that AHR expression is regulated by classical hormones and by its own ligands in granulosa cells.

estradiol, follicle-stimulating hormone, granulosa cells, ovary, toxicology


FOOTNOTES

1 Supported by grants form the ANPCYT PICT 05–09044 and UBACYT X218. J.L.B. is an established investigator from the CONICET.

2 Correspondence: J.L. Baranao, Vuelta de Obligado 2490, 1428 Buenos Aires, Argentina. FAX: 05411 4786–2564; lbaranao{at}dna.uba.ar







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Copyright © 2006 by the Society for the Study of Reproduction.