Amateau and McCarthy's findings published in Nature Neuroscience (June 2004) are noteworthy for suggesting a role for prostaglandins in sexual development. However, evidence suggests that in manipulating PGE2, they unknowingly implicated 3alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.50], 3(or 17)alpha-hydroxysteroid dehydrogenase [E.C. 1.1.1.209] and their respective products, androsterone (ADT) and epitestosterone (EpiT), in the developmental masculinization of sex behavior. EpiT is generally regarded as a hormonally inactive 17alpha-epimer of testosterone (T). In rats, the kidney is the primary site of EpiT formation, whereas in humans it originates from the gonads, with only a small contribution secreted by the adrenals. Because the ratio of T to EpiT is nearly constant, it is presently used for assessing steroid abuse in competitive sports, where the World Anti-Doping Agency (WADA) considers a T/EpiT ratio >4 evidence of T doping. Despite its central role in the detection of illict anabolic steroid use, our knowledge of factors effecting EpiT production is poor. Clues in the literature, however, reveal that prostaglandin-mediated processes, such as LHRH release, may influence its production. Antimycotics, NSAIDs, and opioid analgesics used in sports medicine are all known to effect prostaglandin E2 synthesis. Primary PGs are potent inhibitors of ADT oxidation, while indomethacin, a prostaglandin blocker, powerfully inhibits 3alpha-HSD reduction and ADT oxidation. This is significant because ADT inhibits the oxidation of EpiT, and may modulate its antiandrogenic and neuroprotective effects. It is hypothesized that the T/EpiT ratio is increased by COX-2 inhibitors and opiod analgesics, and decreased by antimycotics that do not impair testosterone biosynthesis. Given the devastating personal and career consequences that may result from false positive drug tests, substantive research on the effects of PGE2 manipulations on EpiT is warranted.

译文

Amateau和McCarthy发表在《自然神经科学》 (2004年6月) 上的发现值得注意,因为它暗示了前列腺素在性发育中的作用。然而,有证据表明,在操纵PGE2时,他们在不知不觉中涉及3α-羟基类固醇脱氢酶 [E.C. 1.1.1.50],3 (或17) α-羟基类固醇脱氢酶 [E.C.1.1.209] 及其各自的产物,雄酮 (ADT) 和表甾酮 (EpiT),在性行为的发展男性化中。EpiT通常被认为是睾丸激素 (T) 的激素不活跃的17α-epimer。在大鼠中,肾脏是EpiT形成的主要部位,而在人类中,肾脏起源于性腺,肾上腺仅分泌少量。由于T与EpiT的比率几乎是恒定的,因此目前用于评估竞技运动中的类固醇滥用,世界反兴奋剂机构 (WADA) 认为T/EpiT比率> 4是T掺杂的证据。尽管它在检测合成代谢类固醇的使用中起着核心作用,但我们对影响epi产生的因素的了解却很差。然而,文献中的线索表明,前列腺素介导的过程 (例如LHRH释放) 可能会影响其产生。运动医学中使用的抗真菌药,NSAIDs和阿片类镇痛药都可以影响前列腺素E2的合成。初级pg是ADT氧化的有效抑制剂,而前列腺素阻滞剂吲哚美辛则有效抑制3α-hsd还原和ADT氧化。这很重要,因为ADT抑制EpiT的氧化,并可能调节其抗雄激素和神经保护作用。假设COX-2抑制剂和阿片类镇痛药会增加T/EpiT比,而不会损害睾丸激素生物合成的抗真菌药会降低T/EpiT比。鉴于假阳性药物测试可能会导致毁灭性的个人和职业后果,因此有必要对PGE2操作对EpiT的影响进行实质性研究。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录