Wilson J D, Griffin J E, Leshin M, George F W
Hum Genet. 1981;58(1):78-84. doi: 10.1007/BF00284153.
Male and female embryos develop in an identical fashion during the initial portion of gestation. If the indifferent gonad differentiates into an ovary (or if no gonad is present), a female phenotype is formed. Male phenotypic differentiation, however, requires the presence of an endocrinologically active testis. Two secretions of the fetal testis, Müllerian inhibiting substance and testosterone, are responsible for male development. Studies of single gene mutations that interfere with androgen action indicate that testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens, and seminal vesicle, whereas the testosterone metabolite dihydrotestosterone induces development of the prostate and male external genitalia. Thus, impairment of dihydrotestosterone formation results in a characteristics phenotype consisting of predominantly female external genitalia but normally virilized Wolffian ducts. The molecular mechanisms by which testosterone and dihydrotestosterone act during fetal development appear to involve the same high affinity receptor, a protein that transports both testosterone and dihydrotestosterone to the nucleus of target cells. When this receptor is either absent, deficient, or structurally abnormal, the actions of both testosterone and dihydrotestosterone are impaired, and the resulting developmental anomalies involve both internal and external genital structures.
在妊娠初期，男性和女性胚胎以相同的方式发育。如果未分化的性腺分化为卵巢（或者没有性腺），则会形成女性表型。然而，男性表型的分化需要有内分泌活性的睾丸存在。胎儿睾丸的两种分泌物，即苗勒管抑制物质和睾酮，负责男性的发育。对干扰雄激素作用的单基因突变的研究表明，睾酮本身负责将沃尔夫管系统发育为附睾、输精管和精囊，而睾酮代谢产物双氢睾酮诱导前列腺和男性外生殖器的发育。因此，双氢睾酮形成的受损会导致一种特征性表型，主要表现为女性外生殖器，但沃尔夫管通常发育正常。睾酮和双氢睾酮在胎儿发育过程中起作用的分子机制似乎涉及同一种高亲和力受体，该蛋白将睾酮和双氢睾酮都转运到靶细胞的细胞核中。当这种受体缺失、不足或结构异常时，睾酮和双氢睾酮的作用都会受损，由此产生的发育异常涉及内外生殖器结构。
