ROLE OF GONADAL-HORMONES IN DEVELOPMENT OF THE SEXUAL PHENOTYPES
ROLE OF GONADAL-HORMONES IN DEVELOPMENT OF THE SEXUAL PHENOTYPES
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DOI：
10.1007/bf00284153
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发表时间：
1981-01-01
期刊：
影响因子：
5.3
通讯作者：
GEORGE, FW
中科院分区：
文献类型：
--
作者：
WILSON, JD;GRIFFIN, JE;GEORGE, FW
男性和女性胚胎在妊娠的最初阶段以相同的方式发育。如果中性性腺分化成卵巢（或者没有性腺），则形成雌性表型。然而，男性表型分化需要内分泌活性睾丸的存在。胎儿睾丸的两种分泌物，苗勒管抑制物质和睾酮，负责男性发育。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Wolffian导管系统男性化为附睾、输精管和精囊，而睾酮代谢物二氢睾酮诱导前列腺和男性外生殖器的发育。因此，双氢睾酮形成障碍导致特征性表型，主要由女性外生殖器组成，但通常男性化的沃尔夫管。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相同的高亲和力受体，一种将睾酮和双氢睾酮转运到靶细胞核的蛋白质。当这种受体缺失、缺乏或结构异常时，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部和外部生殖器结构。
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 secretion 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 characteristic 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.