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人神经母细胞瘤细胞系SH-SY5Y中的睾酮和孕酮代谢

Testosterone and progesterone metabolism in the human neuroblastoma cell line SH-SY5Y.

作者信息

Melcangi R C, Maggi R, Martini L

机构信息

Department of Endocrinology, University of Milano, Italy.

出版信息

J Steroid Biochem Mol Biol. 1993 Dec;46(6):811-8. doi: 10.1016/0960-0760(93)90323-o.

DOI:10.1016/0960-0760(93)90323-o
PMID:8274416
Abstract

The ability of the human neuroblastoma cell line SH-SY5Y to metabolize androgens and progesterone was studied by incubating the cells in the presence of labeled testosterone (T) or progesterone (P) to measure, respectively, the formation of dihydrotestosterone (DHT) or dihydroprogesterone (DHP) (5 alpha-reductase activity). The 3 alpha-hydroxysteroid dehydrogenase activity was studied by evaluating the conversion of labeled DHT into 5 alpha-androstan-3 alpha, 17 beta-diol (3 alpha-diol). The results show that undifferentiated neuroblastoma cells possess a significant 5 alpha-reductase activity, as shown by the considerable conversion of T into DHT; moreover, this enzymatic activity seems to be significantly stimulated following cell differentiation induced by the phorbol ester TPA, but not after differentiation induced by retinoic acid (RA). The 5 alpha-reductase(s) present in SH-SY5Y cells is also able to convert P into DHP. In undifferentiated cells, this conversion was about 8 times higher than that of T into DHT. Under the influences of TPA and RA, the formation of DHP followed the same pattern observed for the formation of DHT. SH-SY5Y cells also appear to possess the enzyme 3 alpha-hydroxysteroid dehydrogenase, since they are able to convert DHT into 3 alpha-diol. This enzymatic activity is not altered following TPA-induced differentiation and appears to be decreased following treatment with RA. It is suggested that the SH-SY5Y cell line may represent a useful "in vitro" model for the study of the mechanisms involved in the control of androgen and P metabolism in nervous cells.

摘要

通过在标记的睾酮(T)或孕酮(P)存在下培养人神经母细胞瘤细胞系SH-SY5Y,分别测量二氢睾酮(DHT)或二氢孕酮(DHP)的形成(5α-还原酶活性),研究了该细胞系代谢雄激素和孕酮的能力。通过评估标记的DHT向5α-雄甾烷-3α,17β-二醇(3α-二醇)的转化来研究3α-羟基类固醇脱氢酶活性。结果表明,未分化的神经母细胞瘤细胞具有显著的5α-还原酶活性,T大量转化为DHT即表明了这一点;此外,这种酶活性在佛波酯TPA诱导的细胞分化后似乎受到显著刺激,但在视黄酸(RA)诱导的分化后则没有。SH-SY5Y细胞中存在的5α-还原酶也能够将P转化为DHP。在未分化细胞中,这种转化比T转化为DHT的转化率高约8倍。在TPA和RA的影响下,DHP的形成遵循与DHT形成相同的模式。SH-SY5Y细胞似乎也具有3α-羟基类固醇脱氢酶,因为它们能够将DHT转化为3α-二醇。这种酶活性在TPA诱导的分化后没有改变,在用RA处理后似乎降低。有人提出,SH-SY5Y细胞系可能代表一种有用的“体外”模型,用于研究神经细胞中雄激素和P代谢控制所涉及的机制。

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