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This version published online on February 10, 2005
Endocrinology, doi:10.1210/en.2004-1272
A more recent version of this article appeared on May 1, 2005
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*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CAMPHOR
*ESTRADIOL

Submitted on September 27, 2004
Accepted on January 24, 2005

Estrogen Target Gene Regulation and Coactivator Expression in Rat Uterus after Developmental Exposure to the UV Filter 4-Methylbenzylidene Camphor

Stefan Durrer, Kirsten Maerkel, Margret Schlumpf, and Walter Lichtensteiger*

Institute of Pharmacology and Toxicology, University of Zurich, CH-8057 Zurich

* To whom correspondence should be addressed. E-mail: lichtens{at}pharma.unizh.ch.

Since the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of non-classical ER agonists. UV filters from cosmetics represent new classes of endocrine active chemicals, including the preferential ER{beta} ligands 4-methylbenzylidene camphor (4-MBC) and 3-benzylidene camphor (3-BC). We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, 47 mg/kg/day) administered in feed to the parent generation before mating, during pregnancy and lactation, and to the offspring until adulthood. 4-MBC altered steady-state levels of mRNAs encoding for ER{alpha}, ER{beta}, progesterone receptor (PR), insulin-like growth factor I (IGF-I), androgen receptor (AR), determined by real-time RT PCR in uterus of 12 week-old offspring. Western blot analyses of the same tissue homogenates indicated changes in ER{alpha} and PR but not ER{beta} proteins. To assess sensitivity to estradiol (E2), offspring were ovariectomized on day 70, injected with E2 (10 or 50 µg/kg sc) on day 84, and killed 6 h later. Acute up-regulation of PR and IGF-I, and down-regulation of ER{alpha} and AR by E2 was dose-dependently reduced in 4-MBC-exposed rats. The reduced response to E2 was accompanied by reduced coactivator SRC-1 mRNA and protein levels. Our data indicate that developmental exposure to 4-MBC affects the regulation of estrogen target genes and the expression of nuclear receptor coregulators in uterus at mRNA and protein levels.


Key words: 4-methylbenzylidene camphor (4-MBC) • development • uterus • mRNA expression • protein expression • SRC-1 • estrogen receptors • progesterone receptor • insulin-like growth factor-I • androgen receptor




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