Labrie Fernand, Martel Céline, Bélanger Alain, Pelletier Georges
Professor Emeritus, Laval University, Quebec City, Canada; Endoceutics Inc, Quebec City, Canada.
Endoceutics Inc, Quebec City, Canada.
J Steroid Biochem Mol Biol. 2017 Apr;168:9-18. doi: 10.1016/j.jsbmb.2016.12.007. Epub 2017 Jan 30.
The objective is to review how the cell-specific amounts of intracellular androgens are all made in women from circulating dehydroepiandrosterone (DHEA) in each peripheral tissue, independently from the rest of the body. Following 500 million years of evolution, approximately three dozen cell-specific intracrine enzymes have been engineered in human peripheral tissues whereby the inactive sex steroid precursor DHEA mainly of adrenal origin is transformed into the appropriate minute intracellular amounts of androgens. These intracellular androgens are inactivated in the same cells, with no biologically significant release of active androgens in the circulation. The best estimate is that approximately 50% as much androgens are synthesized in women, compared to men of the same age. The problem with DHEA, however, the exclusive source of androgens in women of all ages, is that DHEA secretion has already decreased by an average of 60% at time of menopause and continues to decrease thereafter. The human-specific and highly sophisticated mechanisms of intracrinology permit each cell to control androgen availability according to its own needs independently from the remaining of the body. Such a mechanism is completely different from classical endocrinology well understood in men where testosterone of testicular origin is transported through the blood and has indiscriminate access to the androgen receptor (AR) in all AR-containing cells of the body. In men, both the endocrine and intracrine mechanisms are in operation while, in women, only the intracrine mechanisms responsible for intracellular formation from DHEA provide androgens.
目的是回顾女性外周组织中细胞特异性的细胞内雄激素是如何由循环中的脱氢表雄酮(DHEA)独立于身体其他部位产生的。经过5亿年的进化,人类外周组织中设计出了大约三十多种细胞特异性的内分泌酶,通过这些酶,主要来源于肾上腺的无活性性类固醇前体DHEA被转化为适量的细胞内微量雄激素。这些细胞内雄激素在同一细胞内失活,不会向循环中释放具有生物学意义的活性雄激素。最佳估计是,与同年龄男性相比,女性合成的雄激素量约为男性的50%。然而,DHEA作为所有年龄段女性雄激素的唯一来源,问题在于,在绝经时DHEA分泌平均已减少60%,且此后还会继续减少。人类特有的高度复杂的内分泌学机制使每个细胞能够根据自身需求独立于身体其他部位来控制雄激素的可利用性。这种机制与男性中熟知的经典内分泌学完全不同,在男性中,睾丸来源的睾酮通过血液运输,可随意进入体内所有含有雄激素受体(AR)的细胞。在男性中,内分泌和内分泌机制都在起作用,而在女性中,只有负责从DHEA进行细胞内形成的内分泌机制提供雄激素。