THE BIOLOGICAL-ACTIVITY OF 7-ALPHA-METHYL-19-NORTESTOSTERONE IS NOT AMPLIFIED IN MALE REPRODUCTIVE-TRACT AS IS THAT OF TESTOSTERONE
THE BIOLOGICAL-ACTIVITY OF 7-ALPHA-METHYL-19-NORTESTOSTERONE IS NOT AMPLIFIED IN MALE REPRODUCTIVE-TRACT AS IS THAT OF TESTOSTERONE
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DOI：
10.1210/en.130.6.3677
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发表时间：
1992-06-01
期刊：
影响因子：
4.8
通讯作者：
SUNDARAM, K
中科院分区：
文献类型：
--
作者：
KUMAR, N;DIDOLKAR, AK;SUNDARAM, K
基于睾酮而不是7-α-甲基-雄激素在前列腺和精囊中的5-α-位减少的前提，在去势大鼠中研究了这些雄激素的差异生物活性。7-α-甲基-19-去甲睾酮醋酸酯（MENT）增加去势大鼠腹侧前列腺和精囊重量的能力是睾酮的4倍，而其对球海绵体肌和提肛肌（肌肉）重量的影响是睾酮的10倍。在抑制血清促性腺激素水平方面，MENT也比睾酮强约12倍。维持血清促性腺激素水平和肌肉质量的睾酮剂量也维持去势大鼠的前列腺和精囊重量。相比之下，维持肌肉和促性腺激素的剂量的MENT不能维持前列腺和精囊。其他7-α-甲基化雄激素的作用与MENT相似。通过使用5-α-还原酶抑制剂证实了5-α-还原酶在睾酮和MENT对前列腺的差异作用中的重要性。5-α-还原酶抑制剂（N，N-二乙基-3-氧代-4-氮杂-5-α-雄甾-1-烯-17-β-甲酰胺）可显著抑制腹侧前列腺和精囊中的睾酮活性，但对肌肉无抑制作用。然而，酶抑制剂对两种组织上的MENT活性没有影响。相反，醋酸环丙孕酮，一种竞争性结合雄激素受体的抗雄激素，抑制MENT和睾酮对前列腺和肌肉的作用。总之，这些观察结果表明，7-α-甲基化雄激素可以维持雄激素缺乏大鼠的肌肉质量和正常的促性腺激素水平，而不会过度刺激前列腺。这些发现表明，7-α-甲基化雄激素可能为需要雄激素治疗的男性提供一些健康益处。
Based on the premise that testosterone, but not 7-alpha-methyl-androgens, is reduced at the 5-alpha-position in the prostate and seminal vesicles, the differential bioactivities of these androgens were investigated in castrated rats. The ability of 7-alpha-methyl-19-nortestosterone acetate (MENT) to increase the weights of ventral prostate and seminal vesicles of castrated rats was four times higher than that of testosterone, while its effect on the weights of bulbocavernosus plus levator ani muscles (muscle), was 10 times that of testosterone. MENT was also approximately 12 times more potent than testosterone in the suppression of serum gonadotropin levels. A dose of testosterone that maintains serum gonadotropin levels and muscle mass also maintains prostate and seminal vesicle weights in castrated rats. By contrast, a dose of MENT that maintains muscle and gonadotropins does not maintain prostate and seminal vesicles. The action of other 7-alpha-methylated androgens were similar to that of MENT. The importance of 5-alpha reductase in the differential action of testosterone and MENT on prostate was confirmed by using a 5-alpha-reductase inhibitor. The activity of testosterone was significantly suppressed in the ventral prostate and seminal vesicles but not on muscle by the 5-alpha-reductase inhibitor (N,N-diethyl-3-oxo-4-aza-5-alpha-androst-1-ene-17-beta-carboxamide). The enzyme inhibitor, however, had no influence on the activity of MENT on either tissue. In contrast, cyproterone acetate, an antiandrogen that competitively binds to the androgen receptors, inhibited the action of MENT and of testosterone on the prostate as well as on the muscle. In conclusion, these observations show that 7-alpha-methylated androgens can maintain muscle mass and normal gonadotropin levels in androgen deficient rats without hyperstimulating the prostate. These findings suggest that 7-alpha-methylated androgens may offer some health benefits to men who require androgen treatment.