The mechanism of phenotypic sex differentiation

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

Research output: Contribution to journalArticlepeer-review

4 Scopus citations


For the first 2 months of gestation, there is no difference in the development of male and female embryos. Gonadal differentiation then ensues, and the ovary and testis commence to synthesize their characteristic hormones at approximately the same time. The initial secretion of testosterone by the fetal testis and 17β‐estradiol by the fetal ovary appears to be independent of gonadotropin control. If an ovary or no gonad is present, the resulting phenotype is female; thus no gonadal hormones appear to be required for female development. In contrast, two secretions of the fetal testis are responsible for the imposition of the male phenotype. Mullerian regression factor, a poorly characterized peptide hormone, is responsible for suppression of the mullerian ducts, and testosterone accounts for the remainder of male development. The mechanisms by which testosterone causes this differentiative process have been deduced from studies in humans and animals of single gene mutations that interfere with androgen action. Testosterone itself is responsible for virilization of the wolffian ducts into the epididymis, vas deferens, and seminal vesicles, whereas the testosterone metabolite dihydrotestosterone induces the development of the male urethra and external genitalia. Both testosterone and dihydrotestosterone act by combining in the cell cytosol with a high affinity receptor protein that is translocated to the cell nucleus. In summary, chromosomal sex determines gonadal sex, and gonadal sex in turn dictates phenotypic sex.

Original languageEnglish (US)
Pages (from-to)1274-1283
Number of pages10
JournalArthritis & Rheumatism
Issue number11
StatePublished - Nov 1979

ASJC Scopus subject areas

  • Immunology and Allergy
  • Rheumatology
  • Immunology
  • Pharmacology (medical)


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