title: TGFβ1 alters androgenic metabolites and hydroxysteroid dehydrogenase enzyme expression in human prostate reactive stromal primary cells: Is steroid metabolism altered by prostate reactive stromal microenvironment?
abstract: The inflammatory tissue microenvironment can be an active promoter in preneoplastic cancer lesions. Altered steroid hormone metabolism as induced by the inflammatory microenvironment may contribute to epithelial cancer progression. Dehydroepiandrosterone sulfate (DHEAS) is the most abundant endogenous steroid hormone present in human serum and can be metabolized to DHEA, androgens and/or estrogens in peripheral tissues. We have previously reported that TGFβ1-induced reactive prostate stromal cells increase DHEA metabolism to active androgens and alter prostate cancer cell gene expression. While much of the focus on mechanisms of prostate cancer and steroid metabolism is in the epithelial cancer cells, this study focuses on TGFβ1-induced effects on DHEA metabolic pathways and enzymes in human prostate stromal cells. In DHEA-treated primary prostate stromal cells, TGFβ1 produced time- and dose-dependent increases in metabolism of DHEA to androstenedione and testosterone. Also TGFβ1-treated prostate stromal cells exhibited changes in the gene expression of enzymes involved in steroid metabolism including up-regulation of 3β hydroxysteroid dehydrogenase (HSD), and down-regulation of 17βHSD5, and 17βHSD2. These studies suggest that reactive prostate stroma and the inflammatory microenvironment may contribute to altered steroid metabolism and increased intratumoral androgens.
authors.affiliation: Division of Intramural Research, National Center for Complementary and Alternative Medicine, National Institutes of Health, Bethesda, MD 20892, United States.
authors.forename: Yun-shang
authors.initials: YS
authors.lastname: Piao
authors.forename: Paddy
authors.initials: P
authors.lastname: Wiesenfeld
authors.forename: Robert
authors.initials: R
authors.lastname: Sprando
authors.forename: Julia T
authors.initials: JT
authors.lastname: Arnold
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D015096:3-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000735:Androstenedione / Q000378:metabolism; D045744:Cell Line, Tumor; D003687:Dehydroepiandrosterone / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D008297:Male; D011467:Prostate / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism*; D013739:Testosterone / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000494:pharmacology*
chemical_list: D053773:Transforming Growth Factor beta1; D013739:Testosterone; D000735:Androstenedione; D003687:Dehydroepiandrosterone; D015067:17-Hydroxysteroid Dehydrogenases; D015096:3-Hydroxysteroid Dehydrogenases; D006913:Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase
keywords: 17HSD2 or 17HSD5; 17β-hydroxysteroid dehydrogenase type 2 or type 5; 4-dione; 5-diol; 5α-androstanedione; 6S; A-dione; ANOVA; AR; Androstenedione; DHEA; DHEA sulfate; DHEAS; DHT; DMEM; Dulbecco's modified Eagles media; E1; E2; ELISA; FBS; HSD; PrSC; Reactive prostate stroma; S.E.M.; Steroid metabolism; T; TGFβ1; Testosterone; analysis of variance; androgen receptor; androstenediol; androstenedione; cancer-derived primary stromal cells; dehydroepiandrosterone; dihydrotestosterone; enzyme-linked immunosorbent assay; estradiol; estrone; fetal bovine serum; hydroxysteroid dehydrogenase; normal primary prostate stromal cells; standard error of the mean; testosterone; transforming growth factorβ-1