�UroToday.com - Previous fauna studies suggested a role for estrogens in the pathogenesis of benign prostatic hyperplasia (BPH) 1,2. Estrogens interact with 2 forms of estrogen sense organ (ER), ER? and ER?. We of late reported the differential expression of the two ER subtypes in stromal and epithelial cells derived from human BPH tissues 3. We too observed that aromatase enzyme activity converting androgen to estrogen was present in prostate stromal but not epithelial cells in civilization 3. A direct stimulatory effect of estradiol on stromal cells was detected but there was no parallel impression on epithelial cell proliferation in vitro 3. Given the higher up findings, we hypothesized that prostate cells not only respond to estrogen stimulation via the expression of ERs simply are besides capable of modulating such effects by active metamorphosis of estrogens. To date, little is known about the conversion of estrogens to their metabolites in human prostate gland cells.
To establish if prostate cells can metabolise the natural estrogens, estradiol (E2) and estrone (E1), stromal and epithelial cells in primary culture derived from BPH tissues were incubated with 10 nmol/L radiolabeled E2 or E1 for 1-24 hours. Steroids in finish media were then extracted by ethyl group acetate followed by analysis using high-performance liquid chromatography.
Both cell types converted E2 to the weaker estrogen E1 up to 24 hours of incubation but the metabolism was not reversible in these cells. Conversion rate of E2 to E1 during the first 4 hours of incubation was analogue for both stromal (6.1 � 0.7 pmol/mg protein/h; mean � s.e.m. of 3 patients) and epithelial cells (11.9 � 0.7 pmol/mg protein/h). Rate of E2 to E1 conversion in stromal cells was approximately 50% less than that measured in epithelial cells. After extraction of steroids from the civilization media, no radioactivity remained in the aqueous stage, indicating that neither jail cell types conjugate E2 or E1 to water-soluble metabolites in vitro.
To appointment, at least ten different mammalian 17?-hydroxysteroid dehydrogenase (17?HSD types 1 to 10) get been identified, eight of which ar known to have estrogen-metabolizing activities forty-six. 17?HSD subtypes exhibit different substrate specificities; 17?HSD types 1 and 7 feature strong reductase activity converting E1 to E2, whereas types 2, 4, 6, 8, 9 and 10 show variable degrees of dehydrogenase activeness, capable of converting E2 to E1 4-6. Though expression of mRNA or protein of different 17?HSDs has been previously described in human prostate tissues 7-10 and mRNA expression of 17?HSD types 2, 3 and 4 was reported in human prostate cells in primary culture 8,11, to our knowledge, this is the first report card on the metabolism of E2 by oxidative 17?HSD activity in prostate stromal and epithelial cells in primary culture. Both prostate cell types exhibited 17?HSD oxidative activity converting E2 to E1 but no reductase natural process in the opposite direction was detected.
The rates of metamorphosis of E2 to E1 in the present study are comparable to those of the oxidation of testosterone to androstenedione antecedently described in human prostate gland stromal cells in primary culture (3.1 pmol/mg protein/h) 12, possibly by the action at law of 17?HSD type 2. However, it should be borne in mind that the net 17?HSD bodily function measured in cell culture at any point in time is the product of the cumulative activities of the various steroid metabolic enzymes present in the cell at that time. Therefore, the want of conversion of E1 to E2 does non reflect the absence of enzymes adequate to of catalyzing E1 to E2 merely may be due to the dominant enzymatic conditions favoring a relatively high activity of 17?HSD enzymes converting E2 to E1 at the expense of the reductive 17?HSD activity; this results in a net E2 oxidation in these cells. Whether this pattern is also reflected in the in vivo system still remains to be established.
Taken together, the above observations and our late report loan support to the hypothesis that both androgen conversion to oestrogen and oestrogen metabolism in prostate cells can regulate a local estrogenic environment within the prostate.
References
1. Walsh PC and Wilson JD: The induction of prostatic hypertrophy in the dog with androstanediol. J Clin Invest. 57: 1093-7, 1976.
2. DeKlerk DP, Coffey DS, Ewing LL, McDermott IR, Reiner WG, Robinson CH, Scott WW, Strandberg JD, Talalay P, Walsh PC et al.: Comparison of spontaneous and through an experiment induced dogtooth prostatic hyperplasia. J Clin Invest. 64: 842-9, 1979.
3. Ho CK, Nanda J, Chapman KE and Habib FK: Oestrogen and benign prostatic hyperplasia: personal effects on stromal cell proliferation and local formation from androgen. J Endocrinol. 197: 483-91, 2008.
4. Peltoketo H, Luu-The V, Simard J and Adamski J: 17beta-hydroxysteroid dehydrogenase (HSD)/17-ketosteroid reductase (KSR) family; terminology and main characteristics of the 17HSD/KSR enzymes. J Mol Endocrinol. 23: 1-11, 1999.
5. Napoli JL: 17beta-Hydroxysteroid dehydrogenase type 9 and other short-chain dehydrogenases/reductases that catalyze retinoid, 17beta- and 3alpha-hydroxysteroid metabolism. Mol Cell Endocrinol. 171: 103-9, 2001.
6. Yang SY, He XY and Schulz H: Multiple functions of type 10 17beta-hydroxysteroid dehydrogenase. Trends Endocrinol Metab. 16: 167-75, 2005.
7. Elo JP, Akinola LA, Poutanen M, Vihko P, Kyllonen AP, Lukkarinen O and Vihko R: Characterization of 17beta-hydroxysteroid dehydrogenase isoenzyme formulation in benign and malignant human prostate gland. Int J Cancer. 66: 37-41, 1996.
8. Delos S, Carsol JL, Fina F, Raynaud JP and Martin PM: 5alpha-reductase and 17beta-hydroxysteroid dehydrogenase formula in epithelial cells from hyperplastic and malignant human prostate. Int J Cancer. 75: 840-6, 1998.
9. Krazeisen A, Breitling R, Imai K, Fritz S, Moller G and Adamski J: Determination of cDNA, gene structure and chromosomal localisation of function of the novel human 17beta-hydroxysteroid dehydrogenase type 7(1). FEBS Lett. 460: 373-9, 1999.
10. He XY, Merz G, Yang YZ, Pullakart R, Mehta P, Schulz H and Yang SY: Function of human brain scant chain L-3-hydroxyacyl coenzyme A dehydrogenase in androgen metabolism. Biochim Biophys Acta. 1484: 267-77, 2000.
11. Delos S, Carsol JL, Ghazarossian E, Raynaud JP and Martin PM: Testosterone metabolism in primary cultures of human prostate epithelial cells and fibroblasts. J Steroid Biochem Mol Biol. 55: 375-83, 1995.
12. Tsugaya M, Habib FK, Chisholm GD, Ross M, Tozawa K, Hayashi Y, Kohri K and Tanaka S: Testosterone metabolic process in chief cultures of epithelial cells and stroma from benign prostatic hyperplasia. Urol Res. 24: 265-71, 1996.
Written by Clement KM Ho, Jyoti Nanda, Karen E Chapman, and Fouad K Habib, as part of Beyond the Abstract on RPLC263%
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