Mendoza Patricia, Sánchez Catherine, Contreras Héctor R, Vergara Jorge, Acevedo Cristian, Cabezas Juan, Huidobro Christian, Noé Gabriela, Castellón Enrique A
Laboratory of Molecular and Cellular Andrology, Physiology and Biophysics Program, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
Int J Androl. 2009 Dec;32(6):607-15. doi: 10.1111/j.1365-2605.2008.00906.x. Epub 2008 Jul 9.
7-alpha-Methyl-19-Nortestosterone (MENT) is a synthetic androgen more potent than testosterone (T) and cannot be reduced at 5-alpha position. No important effects of MENT on prostate growth have been reported. However, little is known about the effect of MENT on benign prostatic hyperplasia (BPH) or prostate carcinoma (CaP). We evaluate the effect of MENT, T and dihydrotestosterone (DHT) on secretion, proliferation and gene expression of primary cell cultures from human BPH and CaP. Moreover, the effect of these androgens was examined in the presence of finasteride to determine the influence of the 5-alpha reductase (5-AR) activity on the androgenic potency. BPH and CaP primary cultures were treated with 0, 1, 10 and 100 nM of T, MENT or DHT during 24 and 48 h. Prostate-specific antigen (PSA) was measured by micro particles immunoassay and proliferation rate by spectrophotometric assay (MTT) and by the immunochemical detection of the proliferation marker Ki-67. Gene expression of FGF8b (androgen sensitive gene) was evaluated by semi-quantitative RT-PCR. Results showed that MENT treatments increased PSA secretion and proliferation rate with a potency ranged between T and DHT. Similar effects of MENT were observed in both BPH and CaP cultures. The studies with finasteride showed that in BPH and CaP cells, the conversion of T into DHT significantly contributes to its effect on the proliferation and PSA secretion, and corroborated the resistance of MENT to the 5-AR. The effect of MENT on the gene expression of FGF8b in CaP cells was similar to T and lower than DHT. It is concluded that MENT increases proliferative and secretory activities and gene expression on pathological prostate cells although in less extent than the active metabolite DHT. Furthermore, the fall of endogenous concentration of T during MENT treatment anticipates that this androgen will be of low impact for the prostate.
7-α-甲基-19-去甲睾酮（MENT）是一种比睾酮（T）更有效的合成雄激素，且不能在5-α位还原。尚未有关于MENT对前列腺生长有重要影响的报道。然而，关于MENT对良性前列腺增生（BPH）或前列腺癌（CaP）的影响知之甚少。我们评估了MENT、T和双氢睾酮（DHT）对人BPH和CaP原代细胞培养物的分泌、增殖和基因表达的影响。此外，在非那雄胺存在的情况下检测了这些雄激素的作用，以确定5-α还原酶（5-AR）活性对雄激素效力的影响。BPH和CaP原代培养物在24小时和48小时内分别用0、1、10和100 nM的T、MENT或DHT处理。通过微粒免疫测定法测量前列腺特异性抗原（PSA），通过分光光度测定法（MTT）和增殖标志物Ki-67的免疫化学检测来测定增殖率。通过半定量逆转录-聚合酶链反应（RT-PCR）评估成纤维细胞生长因子8b（FGF8b，雄激素敏感基因）的基因表达。结果显示，MENT处理可增加PSA分泌和增殖率，其效力介于T和DHT之间。在BPH和CaP培养物中均观察到MENT的类似作用。非那雄胺研究表明，在BPH和CaP细胞中，T转化为DHT对其增殖和PSA分泌的作用显著，并且证实了MENT对5-AR具有抗性。MENT对CaP细胞中FGF8b基因表达的影响与T相似且低于DHT。结论是，MENT可增加病理性前列腺细胞的增殖和分泌活性以及基因表达，尽管程度低于活性代谢物DHT。此外，MENT治疗期间T的内源性浓度下降预示该雄激素对前列腺的影响较小。
