Estradiol and Bisphenol A stimulate androgen receptor and estrogen receptor gene expression in fetal mouse prostate mesenchyme cells.
BACKGROUND
Hormonal alterations during development have lifelong effects on the prostate gland. Endogenous estrogens, including 17beta-estradiol (E(2)), and synthetic estrogenic endocrine disruptors, such as bisphenol A (BPA), have similar effects on prostate development. Increasing exposure to estrogens within the low-dose, physiologic range results in permanent increases in the size and androgen responsiveness of the prostate, whereas exposure within the high-dose, pharmacologic range has the opposite effects.


OBJECTIVE
We tested the hypothesis that the low-dose effects of estrogens on the developing prostate are associated with increased expression of androgen receptor (Ar) and estrogen receptor 1 (alpha) (Esr1) genes in mesenchyme cells.


METHODS
Ar and Esr1 mRNA levels were quantified in primary cultures of fetal mouse prostate mesenchyme cells treated with E(2) and BPA.


CONCLUSIONS
Ar and Esr1 mRNA expression increased in response to E(2), with thresholds of 0.001 and 0.037 nM, respectively; and in response to BPA, with a threshold of 1 nM for both mRNAs. We did not observe the expected inhibition of Ar mRNA expression by pharmacologic levels of E(2) relative to unexposed cells.


CONCLUSIONS
The observed induction of gene expression occurred at concentrations within the range of free E(2) previously shown to permanently increase prostate size, thus supporting the involvement of direct effects of estrogens on gene expression in prostate mesenchyme. The effects of BPA occurred within the range of concentrations currently measured in human serum, demonstrating the vulnerability of developing tissues to xenoestrogens.
Richter
Catherine A
CA
Division of Biological Sciences, University of Missouri-Columbia, Columbia, Missouri 65211, USA.
Taylor
Julia A
JA
Ruhlen
Rachel L
RL
Welshons
Wade V
WV
Vom Saal
Frederick S
FS
D000704:Analysis of Variance; D000818:Animals; D001559:Benzhydryl Compounds; D017931:DNA Primers / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000494:pharmacology*; D005333:Fetus; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008297:Male; D008648:Mesoderm / Q000187:drug effects*; D051379:Mice; D010636:Phenols / Q000494:pharmacology*; D011467:Prostate / Q000166:cytology*; D011944:Receptors, Androgen / Q000235:genetics / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000098826:Bisphenol A Compounds
D001559:Benzhydryl Compounds; D017931:DNA Primers; D004958:Estradiol; D010636:Phenols; D011944:Receptors, Androgen; D011960:Receptors, Estrogen; C006780:bisphenol A; D000098826:Bisphenol A Compounds