Dr. Weeks’ Comment: Androgen ablation (lowering testosterone) is not a favored treatment protocol and research that prostate cancer is drive-in part by estrogen and not testosterone is intriguing. Of course, testosterone can metabolize to estrogen if one doesn’t take an aromatase inhibitor.

Reprod Toxicol. :Reprod Toxicol. 2007; 23(3): 374–382. Published online 2006 Oct 24. doi: 10.1016/j.reprotox.2006.10.001PMCID: PMC1927084NIHMSID: NIHMS23013PMID: 17123779

Developmental Estrogen Exposures Predispose to Prostate Carcinogenesis with Aging

Gail S. Prins,¹Lynn Birch,¹Wan-Yee Tang,² and  Shuk-Mei Ho²Author informationCopyright and License informationDisclaimerThe publisher’s final edited version of this article is available at Reprod ToxicolSee other articles in PMC that cite the published article.

Abstract

Prostate morphogenesis occurs in utero in humans and during the perinatal period in rodents. While largely driven by androgens, there is compelling evidence for a permanent influence of estrogens on prostatic development. If estrogenic exposures are abnormally high during the critical developmental period, permanent alterations in prostate morphology and function are observed, a process referred to as developmental estrogenization. Using the neonatal rodent as an animal model, it has been shown that early exposure to high doses of estradiol results in an increased incidence of prostatic lesions with aging which include hyperplasia, inflammatory cell infiltration and prostatic intraepithelial neoplasia or PIN, believed to be the precursor lesion for prostatic adenocarcinoma. The present review summarizes research performed in our laboratory to characterize developmental estrogenization and identify the molecular pathways involved in mediating this response. Furthermore, recent studies performed with low-dose estradiol exposures during development as well as exposures to environmentally relevant doses of the endocrine disruptor bisphenol A show increased susceptibility to PIN lesions with aging following additional adult exposure to estradiol. Gene methylation analysis revealed a potential epigenetic basis for the estrogen imprinting of the prostate gland. Taken together, our results suggest that a full range of estrogenic exposures during the postnatal critical period – from environmentally relevant bisphenol A exposure to low-dose and pharmacologic estradiol exposures – results in an increased incidence and susceptibility to neoplastic transformation of the prostate gland in the aging male which may provide a fetal basis for this adult disease.