This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by ORLOWSKI, J. Articles by CLARK, A. F. Search for Related Content PubMed PubMed Citation Articles by ORLOWSKI, J. Articles by CLARK, A. F.

Epithelial- Stromal Interactions in the Regulation of Rat Ventral Prostate Function: Identification and Characterization of Pathways for Androgen Metabolism in Isolated Cell Types^*

JOHN ORLOWSKI and ALBERT F. CLARK

Departments of Biochemistry and Pathology, Queen's University, and Kingston General Hospital Kingston, Ontario, Canada K7L 3N6

Address all correspondence and requests for reprints to: Dr. Albert F. Clark, Department of Biochemistry, Queen's University, Kingston, Ontario, Canada K7L 3N6.

Abstract

Androgen metabolism plays a significant role in the androgen regulation of prostate cell function. In this report the various pathways for androgen metabolism in primary cultures of rat ventral prostate epithelial and stromal cells were identified and characterized by in vitro whole cell assays, using HPLC. Confluent cultures of both cell types were incubated with supraphysiological concentrations (50 nM) of tritiated androgens (testosterone, 5-dihydrotestosterone, 5-androstane-3(and 3β),17β-diols, and ⁴-androstene-3,17-dione), and the metabolites were analyzed at several time points over a 24-h period. The metabolism studies indicated that 5-reductase activity, the oxidative reactions of 3-, 3β), and 17β-hydroxysteroid oxidoreductases, and the reductive reaction of 3β-hydroxysteroid oxidoreductase were expressed at significantly higher levels in epithelial cells compared to stromal cells. The reductive reactions of 3- and 17β-hydroxysteroid oxidoreductases were similar in both cell types. In contrast, stromal cells exhibited substantially higher levels of 6/7-hydroxylase activity. In addition, stromal cells were capable of metabolizing 5adihydrotestosterone directly to a new unidentified polar androgen metabolite (H05-DHT). Overall, epithelial cells were approximately 29 times more capable than stromal cells of forming the biologically active androgen 5-dihydrotestosterone. Conversely, stromal cells were more capable of forming biologically inactive polar androgen metabolites. (Endocrinology 128: 872– 884,1991)

Footnotes

^* This work was supported in part by grants from the Medical Research Council of Canada (MT-2338 and MA-10212).

Department of Molecular Genetics, Biochemistry and Microbiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267.

Received August 16, 1990.

This article has been cited by other articles:

				J. Simard, M.-L. Ricketts, S. Gingras, P. Soucy, F. A. Feltus, and M. H. Melner Molecular Biology of the 3{beta}-Hydroxysteroid Dehydrogenase/{Delta}5-{Delta}4 Isomerase Gene Family Endocr. Rev., June 1, 2005; 26(4): 525 - 582. [Abstract] [Full Text] [PDF]

				G. Pelletier, V. Luu–The, B. Têtu, and F. Labrie Immunocytochemical Localization of Type 5 17ß-Hydroxysteroid Dehydrogenase in Human Reproductive Tissues J. Histochem. Cytochem., June 1, 1999; 47(6): 731 - 738. [Abstract] [Full Text]

				M. El-Alfy, V. Luu-The, X.-F. Huang, L. Berger, F. Labrie, and G. Pelletier Localization of Type 5 17{beta}-Hydroxysteroid Dehydrogenase, 3{beta}-Hydroxysteroid Dehydrogenase, and Androgen Receptor in the Human Prostate by in Situ Hybridization and Immunocytochemistry Endocrinology, March 1, 1999; 140(3): 1481 - 1491. [Abstract] [Full Text]