Expression of enzymes involved in estrogen metabolism in human prostate.
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.
Takase
Yasukazu
Y
Oncology and Molecular Endocrinology Laboratory, CHUL Research Center, 2705 Laurier Boulevard, Québec, G1V 4G2, Canada.
Lévesque
Marie-Hélène
MH
Luu-The
Van
V
El-Alfy
Mohamed
M
Labrie
Fernand
F
Pelletier
Georges
G
D015067:17-Hydroxysteroid Dehydrogenases / Q000096:biosynthesis* / Q000235:genetics; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000096:biosynthesis* / Q000235:genetics; D004967:Estrogens / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D011467:Prostate / Q000201:enzymology* / Q000378:metabolism; D011470:Prostatic Hyperplasia / Q000201:enzymology / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis
D004967:Estrogens; D012333:RNA, Messenger; D015067:17-Hydroxysteroid Dehydrogenases; D001141:Aromatase