EVIDENCE FOR DECREASED ANDROGEN 5-ALPHA-REDUCTION IN SKIN AND LIVER OF MEN WITH SEVERE ACNE AFTER 13-CIS-RETINOIC ACID TREATMENT
EVIDENCE FOR DECREASED ANDROGEN 5-ALPHA-REDUCTION IN SKIN AND LIVER OF MEN WITH SEVERE ACNE AFTER 13-CIS-RETINOIC ACID TREATMENT
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DOI：
10.1210/jc.78.5.1064
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发表时间：
1994-05-01
影响因子：
5.8
通讯作者：
FIET, J
中科院分区：
文献类型：
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作者：
BOUDOU, P;CHIVOT, M;FIET, J
为了研究13-顺式维甲酸（13-cis-RA）治疗对男性重度结节囊肿性痤疮雄激素代谢的影响，8名男性重度痤疮患者在3个月内接受了每日0.7 mg/kg 13-cis-RA的口服给药。在治疗前和治疗结束时，对血清样本、24小时尿液采集和皮肤活检中的雄激素代谢进行了探索，结果显示肾上腺或性腺雄激素的血清水平无显著变化。然而，治疗确实诱导5 α-还原雄激素的血清水平显著降低：5 α-二氢睾酮（P < 0.02）、雄酮葡糖苷酸（P < 0.04）和5 α-雄甾烷-3 α，17 β-二醇葡糖苷酸（P < 0.004）。与血清不同，尿中5 α-还原代谢产物5 α-雄甾烷-3 α，17 β-二醇和雄甾酮没有显著变化，尽管后者的排泄减少。此外，观察到尿中胆烷醇酮排泄量略微显著增加，与雄酮排泄量减少非常相似。13-cis-RA治疗后，雄酮与Etiocholanolone的比值显著降低（P < 0.004），提示肝脏中雄激素5 α-至5 β-还原途径的代谢偏离。在皮肤活检中观察到最明显的效果，其失去了80%的形成5 α-二氢睾酮的能力（P < 0.001）。结论是，13-顺式-RA治疗严重结节囊肿性痤疮的男性不改变性腺或肾上腺功能，但它确实诱导1）通过皮肤活组织检查的5 α-二氢睾酮形成的高度显著降低; 2）血清5 α-二氢睾酮、雄酮葡糖苷酸和5 α-雄甾烷-3 α，17 β-二醇葡糖苷酸的显著降低;最后，3）肝脏雄激素5 α-至5 β-还原途径的偏离。13-顺式-RA治疗对严重痤疮的作用与主要在皮肤中观察到的雄激素5 α减少的显著减少一致。
To investigate the effect of 13-cis-retinoic acid (13-cis-RA) treatment on androgen metabolism in men with severe nodulocystic acne, eight men with severe acne received an oral daily dose of 0.7 mg/kg 13-cis-RA over 3 months. Exploration of androgen metabolism in serum samples, 24-h urine collections, and skin biopsies obtained before and at the end of the treatment revealed no significant alterations in serum levels of either adrenal or gonadal androgens. However, the treatment did induce significant decreases in serum levels of the 5 alpha-reduced androgens: 5 alpha-dihydrotestosterone (P < 0.02), androsterone glucosiduronate (P < 0.04), and 5 alpha-androstan-3 alpha,l7 beta-diol glucosiduronate (P < 0.004). Unlike serum, the urinary 5 alpha-reduced metabolites 5 alpha-androstan-3 alpha,17 beta-diol and androsterone did not vary significantly despite a decrease in the excretion of the latter. Moreover, a marginally significant increase in urinary excretion of etiocholanolone, very similar to the decrease in androsterone excretion, was observed. The ratio of androsterone to etiocholanolone decreased significantly (P < 0.004) after 13-cis-RA therapy and suggested a metabolic deviation from the androgen 5 alpha- to 5 beta-reduction pathway in the liver. The most pronounced effect was observed in skin biopsies, which lost 80% of their ability to form 5 alpha-dihydrotestosterone (P < 0.001). It is concluded that 13-cis-RA therapy in men with severe nodulocystic acne did not alter gonadal or adrenal functions, but it did induce 1) a highly significant decrease in 5 alpha-dihydrotestosterone formation by skin biopsies; 2) significant decreases in serum 5 alpha-dihydrotestosterone, androsterone glucosiduronate, and 5 alpha-androstan-3 alpha,17 beta-diol glucosiduronate; and, finally, 3) deviation of the liver androgen 5 alpha- to 5 beta-reduction pathway. The effect of 13-cis-RA treatment on severe acne is consistent with the dramatic decrease in androgen 5 alpha-reduction observed mainly in the skin.