Regulation of steroid hydroxylase CYP7B1 by androgens and estrogens in prostate cancer LNCaP cells.
The present study reports effects of androgens and estrogens on human CYP7B1 transcription in prostate cancer LNCaP cells. Studies with rodents have suggested a role for the CYP7B1 enzyme in balancing cellular hormone levels important for prostate growth. Little is, however, known about the regulation of human CYP7B1. The current study showed strong suppression of a human CYP7B1 luciferase reporter gene by dihydrotestosterone (DHT) in prostate cancer LNCaP cells. Also, DHT and overexpression of androgen receptor (AR) suppressed CYP7B1 promoter activity and CYP7B1-mediated catalysis in kidney-derived HEK293 cells. Effects on CYP7B1 transcription were observed also by estrogen receptors (ER). The effects appeared different for different estrogens. CYP7B1 was stimulated by synthetic ER agonists but suppressed by 17beta-estradiol and 5alpha-androstane-3beta,17beta-diol in LNCaP cells. Our data indicate an important role for CYP7B1 in balancing prostate hormone levels in human cells. In particular, the data suggest that androgens may control intraprostatic levels of estrogen via regulation of CYP7B1-mediated metabolism.
Tang
Wanjin
W
Department of Pharmaceutical Biosciences, Division of Biochemistry, University of Uppsala, Box 578, S-751 23 Uppsala, Sweden.
Norlin
Maria
M
D000728:Androgens / Q000008:administration & dosage*; D045744:Cell Line, Tumor; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism*; D000072474:Cytochrome P450 Family 7; D004305:Dose-Response Relationship, Drug; D004967:Estrogens / Q000008:administration & dosage*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*
D000728:Androgens; D004967:Estrogens; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D000072474:Cytochrome P450 Family 7; C499571:CYP7B1 protein, human