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Androgen resistance in squirrel monkeys (Saimiri spp.).

机译:松鼠猴(Saimiri spp。)对雄激素的抵抗力。

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The goal of this study was to understand the basis for high androgen levels in squirrel monkeys (Saimiri spp.). Mass spectrometry was used to analyze serum testosterone, androstenedione, and dihydrotestosterone of male squirrel monkeys during the nonbreeding (n = 7) and breeding (n = 10) seasons. All hormone levels were elevated compared with those of humans, even during the nonbreeding season; the highest levels occurred during the breeding season. The ratio of testosterone to dihydrotestosterone in squirrel monkeys is high during the breeding season compared to man. Squirrel monkeys may have high testosterone to compensate for inefficient metabolism to dihydrotestosterone. We also investigated whether squirrel monkeys have high androgens to compensate for low-activity androgen receptors (AR). The response to dihydrotestosterone in squirrel monkey cells transfected with AR and AR-responsive reporter plasmids was 4-fold, compared with 28-fold in human cells. This result was not due to overexpression of cellular FKBP51, which causes glucocorticoid and progestin resistance in squirrel monkeys, because overexpression of FKBP51 had no effect on dihydrotestosterone-stimulated reporter activity in a human fibroblast cell line. To test whether the inherently low levels of FKBP52 in squirrel monkeys contribute to androgen insensitivity, squirrel monkey cells were transfected with an AR expression plasmid, an AR-responsive reporter plasmid, and a plasmid expressing FKBP52. Expression of FKBP52 decreased the EC50 or increased the maximal response to dihydrotestosterone. Therefore, the high androgen levels in squirrel monkeys likely compensate for their relatively low 5 alpha-reductase activity during the breeding season and AR insensitivity resulting from low cellular levels of FKBP52.
机译:这项研究的目的是了解松鼠猴(Saimiri spp。)高雄激素水平的基础。在非繁殖期(n = 7)和繁殖期(n = 10),质谱用于分析雄性松鼠猴的血清睾丸激素,雄烯二酮和二氢睾丸酮。即使在非繁殖季节,所有激素水平都比人类升高。最高水平发生在繁殖季节。与人相比,在繁殖季节,松鼠猴中睾丸激素与二氢睾丸激素的比例较高。松鼠猴可能含有较高的睾丸激素,以补偿二氢睾丸激素的无效代谢。我们还调查了松鼠猴是否具有高雄激素来补偿低活性雄激素受体(AR)。转染了AR和AR反应性报告基因质粒的松鼠猴细胞对二氢睾丸激素的反应是人类细胞的28倍,是4倍。该结果并非归因于细胞FKBP51的过表达,而FKBP51的过表达对人类成纤维细胞系中双氢睾丸激素刺激的报告基因活性没有影响,因此会导致松鼠猴对糖皮质激素和孕激素的抵抗。为了测试松鼠猴中固有的低水平FKBP52是否引起雄激素不敏感,用AR表达质粒,AR应答报告质粒和表达FKBP52的质粒转染松鼠猴细胞。 FKBP52的表达降低EC50或增加对二氢睾丸激素的最大反应。因此,松鼠猴中较高的雄激素水平可能弥补了它们在繁殖季节相对较低的5α-还原酶活性以及由于FKBP52细胞水平低而导致的AR不敏感性。

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