Labrie Fernand, Luu-The Van, Martel Céline, Chernomoretz Ariel, Calvo Ezequiel, Morissette Jean, Labrie Claude
Molecular Endocrinology and Oncology Laboratory, Laval University Hospital Research Center (CRCHUL) and Laval University, Québec City, Canada G1V 4G2.
J Steroid Biochem Mol Biol. 2006 Jul;100(1-3):52-8. doi: 10.1016/j.jsbmb.2006.03.006. Epub 2006 Jun 21.
We have recently taken advantage of the unique power of DNA microarrays to compare the genomic expression profile of tetrahydrogestrinone (THG) with that of dihydrotestosterone (DHT), the most potent natural androgen, thus clearly demonstrating that THG is an anabolic steroid. In 2004, the U.S. Controlled Substances Act has been modified to include androstenedione (4-dione) as an anabolic steroid. However, despite the common knowledge that dehydroepiandrosterone (DHEA) is the precursor of testosterone, DHEA has been excluded from the list of anabolic steroids. We thus used the same DNA microarray technology to analyze the expression profile of practically all the 30,000 genes of the mouse genome modulated by DHEA and DHT in classical androgen-sensitive tissues. Daily subcutaneous injections of DHT (0.1mg) or DHEA (3mg) for 1 month in gonadectomized C57BL6/129 SV mice increased ventral prostate, dorsal prostate, seminal vesicle and preputial gland weight (p<0.01 for all tissues). As early as 24h after single injection of the two steroids, 878, 2681 and 14 probe sets were commonly stimulated or inhibited (p<0.01, change> or =30%), in the prostate (ventral+dorsal), seminal vesicles and preputial glands, respectively, compared to tissues from gonadectomized control animals. After 7 days of daily treatment with DHEA and DHT, 629, 919 and 562 probe sets were commonly modulated in the same tissues while after 27 days of treatment, 1195, 5127 and 2883 probe sets were modulated, respectively. In analogy with the data obtained with THG, the present microarray data provide an extremely precise and unquestionable genomic signature and proof of the androgenic/anabolic activity of DHEA. Such data add to the literature showing that DHEA is transformed into androgens in the human peripheral tissues as well as in laboratory animal species, including the monkey, thus exerting potent androgenic/anabolic activity. The present microarray approach to identify anabolic compounds is applicable to all potential androgenic/anabolic compounds.
我们最近利用DNA微阵列的独特功能，将四氢孕三烯酮（THG）的基因组表达谱与最强效的天然雄激素双氢睾酮（DHT）的基因组表达谱进行了比较，从而清楚地证明THG是一种合成代谢类固醇。2004年，美国《受控物质法》已修订，将雄烯二酮（4-二酮）列为合成代谢类固醇。然而，尽管大家都知道脱氢表雄酮（DHEA）是睾酮的前体，但DHEA却被排除在合成代谢类固醇名单之外。因此，我们使用相同的DNA微阵列技术，分析了经典雄激素敏感组织中几乎所有30000个受DHEA和DHT调节的小鼠基因组基因的表达谱。对去势的C57BL6/129 SV小鼠每日皮下注射DHT（0.1mg）或DHEA（3mg），持续1个月，可增加腹侧前列腺、背侧前列腺、精囊和包皮腺的重量（所有组织p<0.01）。与去势对照动物的组织相比，单次注射这两种类固醇后24小时内，前列腺（腹侧+背侧）、精囊和包皮腺中分别有878、2681和14个探针集受到共同刺激或抑制（p<0.01，变化≥30%）。每日用DHEA和DHT处理7天后，相同组织中有629、919和562个探针集受到共同调节，而处理27天后，分别有1195、5127和2883个探针集受到调节。与用THG获得的数据类似，目前的微阵列数据提供了极其精确且无可置疑的基因组特征，并证明了DHEA的雄激素/合成代谢活性。这些数据补充了文献，表明DHEA在包括猴子在内的人类外周组织以及实验动物物种中可转化为雄激素，从而发挥强大的雄激素/合成代谢活性。目前这种用于鉴定合成代谢化合物的微阵列方法适用于所有潜在的雄激素/合成代谢化合物。
