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Up-regulation of the levels of androgen receptor and its mRNA by androgens in smooth-muscle cells from rat penis

雄激素受体 雄激素 内分泌学 内科学 生物 二氢睾酮 体内 信使核糖核酸 睾酮(贴片) 激素 医学 前列腺癌 癌症 生物化学 基因 生物技术
作者
Néstor F. González-Cadavid,Dolores Vernet,A Fuentes Navarro,José Antonio Rodríguez,Ronald S. Swerdloff,Jacob Rajfer
出处
期刊:Molecular and Cellular Endocrinology [Elsevier]
卷期号:90 (2): 219-229 被引量:58
标识
DOI:10.1016/0303-7207(93)90155-d
摘要

Smooth-muscle cells cultured from the penis of sexually immature (I-PSMC) and adult (A-PSMC) rats express similar high levels of the androgen receptor (AR) mRNA. This contrasts with the marked in vivo decline of both AR mRNA and androgen binding in the penile smooth muscle of adult rats, which appears to be responsible for the cessation of androgen-dependent penile growth upon sexual maturation. PSMC is therefore a good model to study down-regulators of AR expression as a function of cell proliferation in the smooth muscle of androgen-reputative sponsive vascular tissue. In order to determine whether AR protein levels in PSMC correlate with AR mRNA levels, the immunocytochemical detection of ARs and their androgen binding capacity were compared between I- and A-PSMC. The number of ARs and their protein half-lives suggested similar levels of translation of the AR mRNA in both cell lines. The effect of the synthetic analog methyltrienolone (R-1881) on androgen binding was studied in contact-inhibited androgen-deprived PSMC. In contrast to the postulated role of androgens as down-regulators of AR expression in rat penis, ARs were up-regulated in A-PSMC by R-1881. Contact inhibition of A-PSMC combined with serum depletion and androgen deprivation down-regulated AR mRNA levels, and dihydrotestosterone (DHT) counteracted this effect. These results suggest that the loss in A-PSMC of the age-dependent down-regulation of ARs observed in vivo in adult corpora cavernosa smooth muscle is related to the in vitro resumption of cell proliferation and that DHT acts directly on the penile smooth muscle as a positive modulator of AR levels.
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