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大鼠腹侧前列腺上皮细胞和基质细胞培养中的雄激素代谢与作用

Androgen metabolism and actions in rat ventral prostate epithelial and stromal cell cultures.

作者信息

Orlowski J, Clark A F

出版信息

Biochem Cell Biol. 1986 Jun;64(6):583-93. doi: 10.1139/o86-081.

Abstract

The rat ventral prostate requires androgens for normal development, growth, and function. To investigate the relationship between androgen metabolism and its effects in the prostate and to examine differences between the epithelial and stromal cells, we have established a system of primary cell cultures of immature rat ventral prostate cells. Cultures of both cell types after reaching confluency (6-7 days) actively metabolized 3H-labelled testosterone (T), 5 alpha-dihydrotestosterone (5 alpha-DHT), 5 alpha-androstane-3 alpha,17 beta-diol, and 5 alpha-androstane-3 beta,17 beta-diol. The epithelial cells actively reduced T to 5 alpha-DHT and formed significant amounts of 5 alpha-androstane-3,17-dione from T, 5 alpha-DHT, and 5 alpha-androstane-3 alpha,17 beta-diol. All substrates were converted to significant amounts of C19O3 metabolites. The stromal cells also metabolized all substrates, but very little 5 alpha-androstane-3,17-dione was formed. The metabolism studies indicate that both cell types have delta 4-5 alpha-reductase, 3 alpha- and 3 beta-hydroxysteroid oxidoreductase and hydroxylase activities. The epithelial cells have significant 17 beta-hydroxysteroid oxidoreductase activity. The epithelial cells cultures grown in the presence of T have higher acid phosphatase (AP) contents (demonstrated histochemically and by biochemical assay). Tartrate inhibition studies indicate that the epithelial cells grown in the presence of T are making secretory AP. Stromal cell AP is not influenced by T. The results indicate that the cultured cells maintain differentiated prostatic functions: ability to metabolize androgens and, in the case of the epithelial cells, synthesize secretory AP.

摘要

大鼠腹侧前列腺的正常发育、生长和功能需要雄激素。为了研究雄激素代谢与其在前列腺中的作用之间的关系,并检查上皮细胞和基质细胞之间的差异,我们建立了未成熟大鼠腹侧前列腺细胞原代培养体系。两种细胞类型在达到汇合状态(6 - 7天)后,都能积极代谢3H标记的睾酮(T)、5α - 双氢睾酮(5α - DHT)、5α - 雄甾烷 - 3α,17β - 二醇和5α - 雄甾烷 - 3β,17β - 二醇。上皮细胞能将T积极还原为5α - DHT,并从T、5α - DHT和5α - 雄甾烷 - 3α,17β - 二醇中形成大量的5α - 雄甾烷 - 3,17 - 二酮。所有底物都转化为了大量的C19O3代谢物。基质细胞也能代谢所有底物,但形成的5α - 雄甾烷 - 3,17 - 二酮很少。代谢研究表明,两种细胞类型都具有Δ4 - 5α - 还原酶、3α - 和3β - 羟基类固醇氧化还原酶以及羟化酶活性。上皮细胞具有显著的17β - 羟基类固醇氧化还原酶活性。在T存在下生长的上皮细胞培养物具有更高的酸性磷酸酶(AP)含量(通过组织化学和生化分析证实)。酒石酸盐抑制研究表明,在T存在下生长的上皮细胞正在产生分泌性AP。基质细胞的AP不受T的影响。结果表明,培养的细胞保持了分化的前列腺功能:代谢雄激素的能力,以及上皮细胞合成分泌性AP的能力。

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