Vainio S, Heikkilä M, Kispert A, Chin N, McMahon A P
Department of Molecular and Cellular Biology, The BioLabs, Harvard University, Cambridge, Massachusetts 02138, USA.
Nature. 1999 Feb 4;397(6718):405-9. doi: 10.1038/17068.
In the mammalian embryo, both sexes are initially morphologically indistinguishable: specific hormones are required for sex-specific development. Mullerian inhibiting substance and testosterone secreted by the differentiating embryonic testes result in the loss of female (Mullerian) or promotion of male (Wolffian) reproductive duct development, respectively. The signalling molecule Wnt-4 is crucial for female sexual development. At birth, sexual development in males with a mutation in Wnt-4 appears to be normal; however, Wnt-4-mutant females are masculinized-the Mullerian duct is absent while the Wolffian duct continues to develop. Wnt-4 is initially required in both sexes for formation of the Mullerian duct, then Wnt-4 in the developing ovary appears to suppress the development of Leydig cells; consequently, Wnt-4-mutant females ectopically activate testosterone biosynthesis. Wnt-4 may also be required for maintenance of the female germ line. Thus, the establishment of sexual dimorphism is under the control of both local and systemic signals.
在哺乳动物胚胎中，两性最初在形态上无法区分：性别特异性发育需要特定的激素。分化中的胚胎睾丸分泌的苗勒氏管抑制物质和睾酮分别导致雌性（苗勒氏管）的退化或雄性（沃尔夫氏管）生殖管道发育的促进。信号分子Wnt-4对雌性性发育至关重要。出生时，Wnt-4发生突变的雄性的性发育似乎正常；然而，Wnt-4突变的雌性会出现雄性化——苗勒氏管缺失而沃尔夫氏管继续发育。两性最初都需要Wnt-4来形成苗勒氏管，然后发育中的卵巢中的Wnt-4似乎会抑制睾丸间质细胞的发育；因此，Wnt-4突变的雌性会异位激活睾酮的生物合成。维持雌性生殖系可能也需要Wnt-4。因此，性二态性的建立受局部和全身信号的控制。
