Expression of Enzymes Involved in Estrogen Metabolism in Human Prostate

Abstract

There is evidence that estrogens can directly modulate human prostate cell activity. It has also been shown that cultured human prostate cancer LNCaP can synthesize the active estrogen estradiol (E2). To elucidate the metabolism of estrogens in the human prostate, we have studied the expression of enzymes involved in the formation and inactivation of estrogens at the cellular level. 17beta-Hydroxysteroid dehydrogenase (17beta-HSD) types 1, 2, 4, 7, and 12, as well as aromatase mRNA and protein expressions, were studied in benign prostatic hyperplasia (BPH) specimens using in situ hybridization and immunohistochemistry. For 17beta-HSD type 4, only in situ hybridization studies were performed. Identical results were obtained with in situ hybridization and immunohistochemistry. All the enzymes studied were shown to be expressed in both epithelial and stromal cells, with the exception of 17beta-HSD types 4 and 7, which were detected only in the epithelial cells. On the basis of our previous results, showing that 3beta-HSD and 17beta-HSD type 5 are expressed in human prostate, and of the present data, it can be concluded that the human prostate expresses all the enzymes involved in the conversion of circulating dehydroepiandrosterone (DHEA) to E2. The local biosynthesis of E2 might be involved in the development and/or progression of prostate pathology such as BPH and prostate cancer through modulation of estrogen receptors, which are also expressed in epithelial and stromal cells.

Estrogen signaling ability in human endometrial cancer through the cancer-stromal interaction

“…Furthermore, estrogenmetabolizing enzymes such as aromatase, sulfatase, sulfotransferase, and 17b-hydroxysteroid dehydrogenases (17b-HSDs) exist in stromal cells adjacent to the tumor. These convert androgens and inactive estrogens (estrone (E1), estrone sulfate) into active estrogen (17b-estradiol, E 2 ; Pasqualini & Chetrite 2006, Takase et al 2006.…”

“…Aromatase is a key enzyme that catalyses the conversion of androgens to estrogen (Pasqualini & Chetrite 2006, Takase et al 2006. Aromatase mRNA is expressed in various tissues, such as adipose tissue, bone, brain, skin, and breast cancer (Bulun et al 2005).…”

Sex steroids in the tumor microenvironment and prostate cancer progression

“…Tissue aromatase levels in both epithelium and stroma were associated with longer time to biochemical recurrence or disease progression (Grindstad et al 2016). Increased expression of aromatase has been reported in periprostatic adipose tissue, PCa cells and particularly metastatic CRPC (Hiramatsu et al 1997, Ellem et al 2004, Takase et al 2006, Montgomery et al 2008, Celhay et al 2010. Prior clinical trials of aromatase inhibitors in PCa patients showed no benefit (Santen et al 2001, Smith et al 2002.…”

Impact of cows’ milk estrogen on cancer risk

“…The prostate likewise possesses all the necessary enzymes to convert circulating DHEA into estradiol and testosterone, as well as 5a-reductase to convert testosterone to the more bioactive dihydrotestosterone (Takase et al, 2006).…”