| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
ARTICLES |
Medical Research Council Group in Molecular Endocrinology, CHUL Research Center and Laval University, Québec G1V 4G2, Canada
Address all correspondence and requests for reprints to: Dr. Mohamed El-Alfy, Medical Research Council Group in Molecular Endocrinology, CHUL Research Center, 2705 Laurier Boulevard, Québec G1V 4G2, Canada. E-mail address: mohamed.el-alfy{at}crchul.ulaval.ca
An important source of androgens in the human prostate are those synthesized locally from the inactive adrenal precursor dehydroepiandrosterone (DHEA) and its sulfated derivative DHEA-S. Three ß-HSD (hydroxysteroid dehydrogenase) converts DHEA into androstenedione (4-dione), whereas type 5 17ß-HSD catalyzes the reduction of 4-dione into testosterone in the human prostate and other peripheral intracrine tissues. In the present study, we have used two complementary approaches, namely in situ hybridization and immunocytochemistry, to identify the cells that contain the type 5 17ß-HSD messenger RNA and enzyme in human benign prostatic hyperplasia (BPH). Localization of 3ß-HSD and of the androgen receptor (AR) was also investigated by immunostaining in the same tissue. To find out whether there are any differences between BPH and normal prostate tissue, the localization of type 5 17ß-HSD was reexamined by immunocytochemistry in the normal human prostate samples and also in normal prostate epithelial cell line (PrEC). The in situ hybridization results obtained with a tritiated uridine triphosphate (3H-UTP)-labeled type 5 17ß-HSD riboprobe are in agreement with the immunostaining data obtained with a specific antibody to the enzyme. The immunostaining results obtained from normal prostate tissue and BPH were found to be similar. Thus, in the glandular epithelium, basal cells highly express the messenger RNA and the enzyme, whereas luminal cells show a much lower and variable level of expression. In the stroma and walls of blood vessels, fibroblasts and the endothelial cells lining the blood vessels show positive staining. Similar results are observed when the cellular distribution of 3ß-HSD is investigated. AR immunoreactivity, however, shows a different distribution because, in the epithelium, most of the nuclei of basal cells are negative, whereas the majority of nuclei of the luminal cells show positive staining. A strong reaction for AR is also found in most stromal cell nuclei and in the nuclei of most endothelial cells, as well as in some other cells of the walls of blood vessels. In conclusion, human type 5 17ß-HSD, as well as 3ß-HSD, are highly expressed, not only in the basal epithelial cells and stromal fibroblasts but also in the endothelial cells and fibroblasts of the blood vessels. AR, on the other hand, is highly expressed in the luminal cells. The present data suggest that DHEA is transformed in the basal cells of the glandular epithelium into 4-dione by 3ß-HSD and then into testosterone by type 5 17ß-HSD, whereas dihydrotestosterone is synthesized in the luminal cells after diffusion of testosterone from the underlying layer of basal cells. The potential role of androgen formation and action in blood vessels is unknown and opens new avenues of investigation for a better understanding of the multiple roles of androgens.
This article has been cited by other articles:
 |
|
 |
|
  A. Godoy, A. Watts, P. Sotomayor, V. P. Montecinos, W. J. Huss, S. A. Onate, and G. J. Smith Androgen Receptor Is Causally Involved in the Homeostasis of the Human Prostate Endothelial Cell Endocrinology, June 1, 2008; 149(6): 2959 - 2969. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Welzel, N. Wustemann, G. Simic-Schleicher, H. G. Dorr, E. Schulze, G. Shaikh, P. Clayton, J. Grotzinger, P.-M. Holterhus, and F. G. Riepe Carboxyl-Terminal Mutations in 3{beta}-Hydroxysteroid Dehydrogenase Type II Cause Severe Salt-Wasting Congenital Adrenal Hyperplasia J. Clin. Endocrinol. Metab., April 1, 2008; 93(4): 1418 - 1425. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K Wako, T Kawasaki, K Yamana, K Suzuki, S Jiang, H Umezu, T Nishiyama, K Takahashi, T Hamakubo, T Kodama, et al. Expression of androgen receptor through androgen-converting enzymes is associated with biological aggressiveness in prostate cancer J. Clin. Pathol., April 1, 2008; 61(4): 448 - 454. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Chouinard, O. Barbier, and A. Belanger UDP-glucuronosyltransferase 2B15 (UGT2B15) and UGT2B17 Enzymes Are Major Determinants of the Androgen Response in Prostate Cancer LNCaP Cells J. Biol. Chem., November 16, 2007; 282(46): 33466 - 33474. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Qiu, M. Zhou, M. Mazumdar, A. Azzi, D. Ghanmi, V. Luu-The, F. Labrie, and S.-X. Lin Structure-based Inhibitor Design for an Enzyme That Binds Different Steroids: A POTENT INHIBITOR FOR HUMAN TYPE 5 17beta-HYDROXYSTEROID DEHYDROGENASE J. Biol. Chem., March 16, 2007; 282(11): 8368 - 8379. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Q. Ji, L. Chang, F. Z. Stanczyk, M. Ookhtens, A. Sherrod, and A. Stolz Impaired Dihydrotestosterone Catabolism in Human Prostate Cancer: Critical Role of AKR1C2 as a Pre-Receptor Regulator of Androgen Receptor Signaling Cancer Res., February 1, 2007; 67(3): 1361 - 1369. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Takase, M.-H. Levesque, V. Luu-The, M. El-Alfy, F. Labrie, and G. Pelletier Expression of Enzymes Involved in Estrogen Metabolism in Human Prostate J. Histochem. Cytochem., August 1, 2006; 54(8): 911 - 921. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. Le, J. T. Arnold, K. K. McFann, and M. R. Blackman DHT and testosterone, but not DHEA or E2, differentially modulate IGF-I, IGFBP-2, and IGFBP-3 in human prostatic stromal cells Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E952 - E960. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K-M Fung, E N S Samara, C Wong, A Metwalli, R Krlin, B Bane, C Z Liu, J T Yang, J V Pitha, D J Culkin, et al. Increased expression of type 2 3{alpha}-hydroxysteroid dehydrogenase/type 5 17{beta}-hydroxysteroid dehydrogenase (AKR1C3) and its relationship with androgen receptor in prostate carcinoma. Endocr. Relat. Cancer, March 1, 2006; 13(1): 169 - 180. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Stanbrough, G. J. Bubley, K. Ross, T. R. Golub, M. A. Rubin, T. M. Penning, P. G. Febbo, and S. P. Balk Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res., March 1, 2006; 66(5): 2815 - 2825. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. R. Bauman, S. Steckelbroeck, M. V. Williams, D. M. Peehl, and T. M. Penning Identification of the Major Oxidative 3{alpha}-Hydroxysteroid Dehydrogenase in Human Prostate That Converts 5{alpha}-Androstane-3{alpha},17{beta}-diol to 5{alpha}-Dihydrotestosterone: A Potential Therapeutic Target for Androgen-Dependent Disease Mol. Endocrinol., February 1, 2006; 20(2): 444 - 458. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 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]
|
|
|
|
|
|
D M Peehl Primary cell cultures as models of prostate cancer development Endocr. Relat. Cancer, March 1, 2005; 12(1): 19 - 47. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. T. Arnold, H. Le, K. K. McFann, and M. R. Blackman Comparative effects of DHEA vs. testosterone, dihydrotestosterone, and estradiol on proliferation and gene expression in human LNCaP prostate cancer cells Am J Physiol Endocrinol Metab, March 1, 2005; 288(3): E573 - E584. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Quinkler, B. Sinha, J. W Tomlinson, I. J Bujalska, P. M Stewart, and W. Arlt Androgen generation in adipose tissue in women with simple obesity - a site-specific role for 17{beta}-hydroxysteroid dehydrogenase type 5 J. Endocrinol., November 1, 2004; 183(2): 331 - 342. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pelletier, V. Luu-The, S. Li, J. Ouellet, and F. Labrie Cellular Localization of mRNA Expression of Enzymes Involved in the Formation and Inactivation of Hormonal Steroids in the Mouse Prostate J. Histochem. Cytochem., October 1, 2004; 52(10): 1351 - 1356. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Qiu, M. Zhou, F. Labrie, and S.-X. Lin Crystal Structures of the Multispecific 17{beta}-Hydroxysteroid Dehydrogenase Type 5: Critical Androgen Regulation in Human Peripheral Tissues Mol. Endocrinol., July 1, 2004; 18(7): 1798 - 1807. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 I. Franck Lissbrant, E. Lissbrant, A. Persson, J.-E. Damber, and A. Bergh Endothelial Cell Proliferation in Male Reproductive Organs of Adult Rat Is High and Regulated by Testicular Factors Biol Reprod, April 1, 2003; 68(4): 1107 - 1111. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Pelletier Effects of Estradiol on Prostate Epithelial Cells in the Castrated Rat J. Histochem. Cytochem., November 1, 2002; 50(11): 1517 - 1524. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B.-l. Chang, S. L. Zheng, G. A. Hawkins, S. D. Isaacs, K. E. Wiley, A. Turner, J. D. Carpten, E. R. Bleecker, P. C. Walsh, J. M. Trent, et al. Joint Effect of HSD3B1 and HSD3B2 Genes Is Associated with Hereditary and Sporadic Prostate Cancer Susceptibility Cancer Res., March 1, 2002; 62(6): 1784 - 1789. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. Suzuki, A. D. Darnel, J.-I. Akahira, N. Ariga, S. Ogawa, C. Kaneko, J. Takeyama, T. Moriya, and H. Sasano 5{{alpha}}-Reductases in Human Breast Carcinoma: Possible Modulator of in Situ Androgenic Actions J. Clin. Endocrinol. Metab., May 1, 2001; 86(5): 2250 - 2257. [Abstract] [Full Text]
|
|
|
|
|
|
O. Barbier, H. Lapointe, M. El Alfy, D. W. Hum, and A. Bélanger Cellular Localization of Uridine Diphosphoglucuronosyltransferase 2B Enzymes in the Human Prostate by in Situ Hybridization and Immunohistochemistry J. Clin. Endocrinol. Metab., December 1, 2000; 85(12): 4819 - 4826. [Abstract] [Full Text]
|
|
|
|
|
|
New Insight into the Molecular Basis of 3{beta}-Hydroxysteroid Dehydrogenase Deficiency: Identification of Eight Mutations in the HSD3B2 Gene in Eleven Patients from Seven New Families and Comparison of the Functional Properties of Twenty-Five Mutant Enzymes J. Clin. Endocrinol. Metab., December 1, 1999; 84(12): 4410 - 4425. [Abstract] [Full Text]
|
|
|
|
|
|
G. Pelletier, V. Luu-The, A. Charbonneau, and F. Labrie Cellular Localization of Estrogen Receptor Beta Messenger Ribonucleic Acid in Cynomolgus Monkey Reproductive Organs Biol Reprod, November 1, 1999; 61(5): 1249 - 1255. [Abstract] [Full Text]
|
|
|
|
|
|
S. Gingras and J. Simard Induction of 3{beta}-Hydroxysteroid Dehydrogenase/ Isomerase Type 1 Expression by Interleukin-4 in Human Normal Prostate Epithelial Cells, Immortalized Keratinocytes, Colon, and Cervix Cancer Cell Lines Endocrinology, October 1, 1999; 140(10): 4573 - 4584. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
