Submitted April 10, 2006
Returned for revision May 3, 2006
Accepted May 23, 2006
Toxicology
Regulation of Aryl Hydrocarbon Receptor Expression in Rat
Granulosa Cells
Ursula A. Bussmann
and
J. Lino Baranao *
* To whom correspondence should be addressed. E-mail: lbaranao{at}agencia.secyt.gov.ar.
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 down-regulated 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
replenish 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.
Key words:
Ovary •
Toxicology •
Estradiol •
Follicle-stimulating hormone •
Granulosa cells
