Sinisi A A, Pasquali D, Notaro A, Bellastella A
Endocrinology and Medical Andrology Section, Department of Clinical and Experimental Medicine and Surgery, Second University of Naples, Naples, Italy.
J Endocrinol Invest. 2003;26(3 Suppl):23-8.
In humans, like as in other mammals, the gonads, the internal genital ducts, and the external genital structures all develop from bipotential embryologic tissues. Male or female phenotype develops through a cascade of processes which initiate with sex determination and follow with sex differentiation. The karyotype (46, XY or 46, XX) of the embryo (genetic sex) determines whether primordial gonad differentiates into a testis or an ovary, respectively (gonadal differentiation). A Y-related gene, SRY, acts as a switch signal for testis differentiation. Testis development process involves several steps controlled by other non-OY-linked genes, such as Wilms tumor gene 1 (WT1), EMX2, LIM1, steroidogenic factor 1(SF-1), SRY box-related gene 9 (SOX9). Since other genes, such as Wnt-4 and DAX-1, are necessary for the initiation of female pathway in sex determination, female development cannot be considered a default process. Hormonal production of differentiated gonads is relevant for differentiation of the internal and external genitalia during fetal life, and for the development of secondary sex characteristics at puberty. Antimullerian hormone (AMH) secreted by Sertoli cells inhibits the development of female internal genitalia (tube, uterus, upper part of vagina); testosterone secreted by Leydig cells induces stabilization of wolffian ducts and development of internal male genitalia. Differentiation of external male genitalia requires the transformation of testosterone to dihydrotestosterone by 5alpha reductase type 2 expressed in genital skin and urogenital sinus. The effects of androgens occur in presence of functional androgen receptor (AR) protein. Mutations of genes coding for steroidogenic enzymes, AMH, AMH receptor, AR and 5alpha reductase are all associated with impairment of sex differentiation and result in genital ambiguity.
与其他哺乳动物一样，人类的性腺、内生殖管道和外生殖器结构均由具有双向分化潜能的胚胎组织发育而来。男性或女性表型通过一系列过程形成，这些过程始于性别决定，接着是性别分化。胚胎的核型（46，XY或46，XX）（遗传性别）分别决定原始性腺分化为睾丸还是卵巢（性腺分化）。一个与Y染色体相关的基因，即SRY基因，作为睾丸分化的开关信号。睾丸发育过程涉及由其他非Y连锁基因控制的几个步骤，如威尔姆斯瘤基因1（WT1）、EMX2、LIM1、类固醇生成因子1（SF-1）、SRY盒相关基因9（SOX9）。由于其他基因，如Wnt-4和DAX-1，对于性别决定中女性发育途径的启动是必需的，因此不能将女性发育视为默认过程。分化性腺的激素分泌对于胎儿期内、外生殖器的分化以及青春期第二性征的发育至关重要。支持细胞分泌的抗苗勒管激素（AMH）抑制女性内生殖器（输卵管、子宫、阴道上段）的发育；睾丸间质细胞分泌的睾酮诱导中肾管稳定并发育为男性内生殖器。男性外生殖器的分化需要在生殖器皮肤和泌尿生殖窦中表达的2型5α还原酶将睾酮转化为二氢睾酮。雄激素的作用在功能性雄激素受体（AR）蛋白存在的情况下发生。编码类固醇生成酶、AMH、AMH受体、AR和5α还原酶的基因突变均与性别分化受损有关，并导致生殖器模糊不清。
