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

Abstract

Because the estrogen receptor (ER) ligand type influences transactivation, it is important to obtain information on molecular actions of nonclassical 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. We studied estrogen target gene expression in uterus of Long Evans rats after developmental exposure to 4-MBC (0.7, 7, 24, and 47 mg/kg x d) 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), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-wk-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 d 70, injected with E2 (10 or 50 microg/kg sc) on d 84, and killed 6 h later. Acute up-regulation of PR and IGF-I and down-regulation of ER alpha and androgen receptor by E2 were 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.

Convergent transcriptional profiles induced by endogenous estrogen and distinct xenoestrogens in breast cancer cells

“…Epidemiological studies suggest a positive correlation between blood levels of chemicals with estrogenic activity, such as organochlorine pollutants, and breast cancer incidence among women, implying that the growing risk of contracting mammary cancer may be linked to the wide distribution of synthetic xenoestrogens (12,13,(44)(45)(46)(47). On the other hand, beneficial health effects have been attributed to the dietary intake of natural phytoestrogens in food of plant origin (17,18).…”

Vascular endothelial growth factor-A isoform and (co)receptor expression are differentially regulated by 17β-oestradiol in the ovariectomised mouse uterus

“…However, 18S expression increased at the 24-h time point in whole uterine tissue only. Glyceraldehyde 3-phosphate dehydrogenase and b-actin are also common housekeeping genes for quantitative RT-PCR but are known to be regulated by oestrogen (Durrer et al 2005). Therefore, as a known amount of mRNA was used in each reaction, whole uterine mRNA data were analysed without reference to a housekeeping gene to prevent skewing of data at this one time point.…”

Influence of cosmetics vehicles on 4-methylbenzylidene-camphor's skin penetration, in vitro

“…Additionally, 4MBC can be re-absorbed through the skin. Durrer et al, (2005) observed that the 4-MBC altered steady-state levels of mRNAs encoding for ER alpha, ER beta, progesterone receptor (PR), IGF-I, androgen receptor, determined by real-time RT-PCR in uterus of 12-week-old offspring. Hamann et al, (2006) observed that 4-MBC was a potent inhibitor of the pituitary-thyroid-axis due to the fact that TSH serum levels were significantly elevated and the weight of the thyroid glands that was remarkably increased.…”