Young J, Couzinet B, Nahoul K, Brailly S, Chanson P, Baulieu E E, Schaison G
Service d'Endocrinologie et des Maladies de la Reproduction, Hopital Bicêtre, France.
J Clin Endocrinol Metab. 1997 Aug;82(8):2578-85. doi: 10.1210/jcem.82.8.4157.
The physiological importance and therapeutical interest of dehydroepiandrosterone (DHEA) and its sulfate ester (DHEAS) are still controversial. Panhypopituitarism is characterized by the absence of secretion of adrenal and gonadal steroids and thus the production of their metabolites. The conversion of DHEA given orally into delta 5 derivatives, androgens, androgen metabolites, and estrogens was studied in ten patients with complete panhypopituitarism. Sex steroid therapy was withdrawn for at least 2 months. Each patient received, at 1-month intervals and in a random order, two single oral doses of DHEA (50 mg and 200 mg) and placebo. During each treatment, urine samples were collected for 24 h, and blood samples were drawn at hourly intervals for 8 h. In patients with pituitary deficiency, plasma DHEA and DHEAS were not detectable and increased, with the 50 mg dose, up to levels observed in young adults. The administration of 200 mg of DHEA induced an increase of both steroids to supraphysiological plasma levels. A small increase of delta 5-androstenediol was observed. In contrast, the increase of plasma delta 4-androstenedione was important and dose dependent. DHEA was also converted into the potent sex steroid testosterone (T). The administration of a 50 mg dose of DHEA restored plasma T to levels similar to those observed in young women. The 200 mg dose induced an important increase of plasma T, slightly below the levels observed in normal men. The increase of plasma dihydrotestosterone levels was small at both doses of DHEA, in contrast with the large conversion of DHEA into androsterone glucuronide and androstanediol glucuronide. Finally, DHEA administration induced a significant and dose dependent increase of plasma estrogens and particularly of estradiol. In conclusion, this short term study demonstrates that: 1) panhypopituitarism is a model of interest to study the metabolism of DHEA; 2) in the absence of pituitary hormones and of adrenal and gonadal steroids, DHEA given orally is mainly converted into delta 4 derivatives, which in turn are strongly metabolized into 5 alpha-3keto-reduced steroids; 3) a significant increase of sex active hormones was observed in plasma after 200 and even 50 mg of DHEA. Thus, biotransformation of DHEA into potent androgens and estrogens may explain several of the reported beneficial actions of this steroid in aging people.
脱氢表雄酮（DHEA）及其硫酸酯（DHEAS）的生理重要性和治疗意义仍存在争议。全垂体功能减退症的特征是肾上腺和性腺类固醇分泌缺失，因此其代谢产物的生成也缺失。对10例完全性全垂体功能减退症患者口服DHEA转化为Δ5衍生物、雄激素、雄激素代谢产物及雌激素的情况进行了研究。停用性类固醇治疗至少2个月。每位患者每隔1个月随机接受两次口服单剂量DHEA（50mg和200mg）及安慰剂。每次治疗期间，收集24小时尿液样本，并每隔1小时采集血样，共采集8小时。垂体功能减退患者血浆中检测不到DHEA和DHEAS，服用50mg剂量后，其水平升高至年轻人中观察到的水平。服用200mg DHEA可使两种类固醇的血浆水平升高至超生理水平。观察到Δ5 - 雄烯二醇略有增加。相比之下，血浆Δ4 - 雄烯二酮的增加显著且呈剂量依赖性。DHEA还可转化为强效性类固醇睾酮（T）。服用50mg剂量的DHEA可使血浆T恢复至与年轻女性中观察到的水平相似。200mg剂量可使血浆T显著增加，略低于正常男性中观察到的水平。与DHEA大量转化为雄酮葡萄糖醛酸苷和雄烷二醇葡萄糖醛酸苷相比，两种剂量的DHEA使血浆双氢睾酮水平的升高均较小。最后，服用DHEA可使血浆雌激素，尤其是雌二醇显著且呈剂量依赖性增加。总之，这项短期研究表明：1）全垂体功能减退症是研究DHEA代谢的一个有意义的模型；2）在缺乏垂体激素以及肾上腺和性腺类固醇的情况下，口服DHEA主要转化为Δ4衍生物，这些衍生物又会强烈代谢为5α - 3酮还原类固醇；3）服用200mg甚至50mg DHEA后，血浆中具有性活性的激素显著增加。因此，DHEA向强效雄激素和雌激素的生物转化可能解释了该类固醇在老年人中报道的一些有益作用。
