Sexual differentiation: Early hormone synthesis and action

J. D. Wilson, Jim Griffin III, F. W. George

Research output: Contribution to journalReview articlepeer-review

32 Scopus citations


Male and female embryos develop in an identical fashion during the initial phases of gestation and it is only after the gonads differentiate and endocrine function of the testis is initiated that male phenotypic differentiation can occur. If an ovary (or no gonad) is present the final phenotype is female; thus, no gonadal hormones appear to be required for development of the female phenotype. In contrast, two secretions of the fetal testis, Mullerian regression factor and testosterone, are responsible for the formation of the male phenotype. The former, a poorly characterized peptide hormone, is responsible for suppression of the Mullerian ducts. The remainder of male development is due directly or indirectly to testosterone secretion. The onset of testosterone synthesis in the fetal testis takes place just prior to the onset of male phenotypic differentiation and the process appears to be initially independent of gonadotropin control. Studies of single gene mutations that interfere with androgen action have indicated that testosterone itself is responsible for virilization of the Wolffian duct system into the epididymis, vas deferens and seminal vesicles, whereas the testosterone metabolite dihydrotestosterone induces the development of the prostate and male external genitalia. Thus, in 5α-reductase deficiency, an autosomal recessive disorder in which dihydrotestosterone formation is impaired, virilization of the Wolffian ducts is normal, but the external genitalia and urogenital sinus derivatives are female in character. In the X-linked disorders of the androgen receptor, a high affinity receptor necessary for the translocation of both testosterone and dihydrotestosterone into the nucleus is deficient or abnormal, the actions of both hormones are impaired and developmental abnormalities may involve both Wolffian derivatives and the external genitalia as well. In summary, the development of gonadal sex dictates the development of phenotypic sex with androgen secretion by the fetal testis serving as the agent for virilization of the Wolffian ducts, urogenital sinus, and the external genitalia. The molecular mechanisms by which the hormones act during fetal development appear to be the same as those operative in the postnatal state.

Original languageEnglish (US)
Pages (from-to)9-17
Number of pages9
JournalBiology of reproduction
Issue number1
StatePublished - 1980

ASJC Scopus subject areas

  • Reproductive Medicine
  • Cell Biology


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