Bélanger A, Candas B, Dupont A, Cusan L, Diamond P, Gomez J L, Labrie F
Laboratory of Molecular Endocrinology, CHUL Research Center, Quebec, Canada.
J Clin Endocrinol Metab. 1994 Oct;79(4):1086-90. doi: 10.1210/jcem.79.4.7962278.
It is well recognized that aging in men is accompanied by a decline in the serum levels of some adrenal and testicular steroids, but little or no attention has focused on the multiple steroid metabolites that are formed by steroid-converting enzymes in target tissues. In the present study, we have examined in detail the serum concentrations of a large series of adrenal and testicular steroids and their most significant metabolites produced in intracrine peripheral tissues. The serum concentrations of 26 conjugated and unconjugated C21-, C19-, and C18-steroids were measured in 2423 men aged 40-80 yr. The serum concentrations of the major circulating adrenal C19-steroids, namely dehydroepiandrosterone (DHEA) and its sulfate (DHEA-S), androst-5-ene-3 beta, 17 beta-diol and its sulfate, and androstenedione, decreased by about 60% between the ages of 40-80 yr. The small decrease in the serum concentrations of progesterone and pregnenolone in the presence of increased levels of cortisol and markedly decreased levels of DHEA, androst-5-ene-3 beta, 17 beta-diol, and their polar metabolites suggests that adrenal 17,20-lyase is particularly affected by aging. In addition to a marked decline in the serum concentrations of adrenal C19-steroids, a smaller, but significant, decrease occurred in serum testosterone. However, serum dihydrotestosterone levels remained constant, but the glucuronidated derivatives of dihydrotestosterone metabolites (androstane-3 alpha, 17 beta-diol glucuronide, androstane-3 beta, 17 beta-diol glucuronide, and androsterone glucuronide) were reduced by 45-50%, suggesting that 5 alpha-reductase activity in peripheral tissues may show a compensatory increase during aging. Analysis of the fatty acid esters of DHEA (DHEA-FA) also revealed that these nonpolar steroids markedly decrease between 40-80 yr of age, although such a decrease in DHEA-FA levels was smaller than that in DHEA and DHEA-S, suggesting that the formation of DHEA-FA may be specifically increased during aging. In summary, the present study suggests that in contrast to the marked decline in activity of steroidogenic enzymes in the adrenals and the small decrease in the testis, the activity of the steroid-converting enzymes present in peripheral tissues does not decrease during aging. In fact, the marked decrease in DHEA formation by the adrenals leads to a decrease of about 50% in total androgens in men between the ages of 40-80 yr. Such a decrease probably affects many physiological processes during aging.
人们普遍认识到，男性衰老伴随着一些肾上腺和睾丸类固醇血清水平的下降，但很少或几乎没有关注目标组织中由类固醇转化酶形成的多种类固醇代谢物。在本研究中，我们详细检测了一系列肾上腺和睾丸类固醇及其在内分泌外周组织中产生的最重要代谢物的血清浓度。测定了2423名40 - 80岁男性血清中26种结合型和非结合型C21、C19和C18类固醇的浓度。主要循环肾上腺C19类固醇，即脱氢表雄酮（DHEA）及其硫酸盐（DHEA - S）、雄甾 - 5 - 烯 - 3β，17β - 二醇及其硫酸盐以及雄烯二酮的血清浓度在40 - 80岁之间下降了约60%。在皮质醇水平升高以及DHEA、雄甾 - 5 - 烯 - 3β，17β - 二醇及其极性代谢物水平显著降低的情况下，孕酮和孕烯醇酮血清浓度略有下降，这表明肾上腺17,20 - 裂解酶特别受衰老影响。除了肾上腺C19类固醇血清浓度显著下降外，血清睾酮也有较小但显著的下降。然而，血清双氢睾酮水平保持不变，但其代谢物（雄烷 - 3α，17β - 二醇葡萄糖醛酸苷、雄烷 - 3β，17β - 二醇葡萄糖醛酸苷和雄酮葡萄糖醛酸苷）的葡萄糖醛酸化衍生物减少了45 - 50%，这表明外周组织中的5α - 还原酶活性在衰老过程中可能会出现代偿性增加。对DHEA脂肪酸酯（DHEA - FA）的分析还表明，这些非极性类固醇在40 - 80岁之间显著下降，尽管DHEA - FA水平的下降幅度小于DHEA和DHEA - S，这表明DHEA - FA的形成在衰老过程中可能会特异性增加。总之，本研究表明，与肾上腺中类固醇生成酶活性的显著下降和睾丸中较小程度的下降相反，外周组织中存在的类固醇转化酶活性在衰老过程中不会降低。事实上，肾上腺中DHEA生成的显著下降导致40 - 80岁男性总雄激素减少约50%。这种下降可能会影响衰老过程中的许多生理过程。
