title: Autologous down-regulation of androgen receptor messenger ribonucleic acid.
abstract: Autoregulation of androgen receptor (AR) mRNA was investigated using Northern blot analysis with AR cDNA fragments as probes. The amount of AR mRNA increased 2- to 10-fold with androgen withdrawal and decreased below control levels after androgen stimulation in rat ventral prostate, coagulating gland, epididymis, seminal vesicle, kidney, and brain, and in a human prostate cancer cell line, LNCaP. In rat ventral prostate, AR mRNA increased 2- to 3-fold within 24 h after castration and remained elevated for 4 days. Treatment with testosterone propionate beginning 24 h after castration reduced ventral prostate AR mRNA 4-fold within 8 h of androgen replacement. Administration of estradiol 24 h after castration had no significant effect on prostatic AR mRNA. Androgens, including testosterone and the synthetic androgen methyltrienolone (R1881), or the antiandrogen cyproterone acetate down-regulated AR mRNA in vitro in LNCaP cells, whereas estradiol was without effect. Administration of testosterone propionate to rats with androgen insensitivity did not decrease AR mRNA. Down-regulation of AR mRNA by androgen is therefore a receptor-mediated process which occurs in vivo in rat tissues that differ in androgen responsiveness and in cultured human prostate cells.
authors.affiliation: Laboratories for Reproductive Biology, University of North Carolina, Chapel Hill 27599.
authors.forename: V E
authors.initials: VE
authors.lastname: Quarmby
authors.forename: W G
authors.initials: WG
authors.lastname: Yarbrough
authors.forename: D B
authors.initials: DB
authors.lastname: Lubahn
authors.forename: F S
authors.initials: FS
authors.lastname: French
authors.forename: E M
authors.initials: EM
authors.lastname: Wilson
mesh_terms: D000818:Animals; D015152:Blotting, Northern; D015536:Down-Regulation; D006706:Homeostasis; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011944:Receptors, Androgen / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D012333:RNA, Messenger; D011944:Receptors, Androgen