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Autologous Down-Regulation of Androgen Receptor Messenger Ribonucleic Acid

The Laboratories for Reproductive Biology and the Departments of Pediatrics and Pathology, University of North Carolina at Chapel Hill Chapel Hill, North Carolina 27599

Address requests for reprints to: Dr. Elizabeth M. Wilson, University of North Carolina, Laboratories for Reproductive Biology, CB7500, MacNider Building, Chapel Hill, North Carolina 27599.

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 receptormediated process which occurs in vivo in rat tissues that differ in androgen responsiveness and in cultured human prostate cells.

FOOTNOTES

This work was supported by NIH Grants HD-16910, HD- 04466, P30-HD-18968, the Andrew W. Mellon Foundation, and the Pew Scholars Program in the Biomedical Sciences.

Received for publication August 17, 1989. Revision received September 18, 1989. Accepted for publication September 22, 1989.

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