Cultured human skin fibroblasts

a model for the study of androgen action

Terry R. Brown, Claude J. Migeon

Research output: Contribution to journalArticle

Abstract

Human skin may be considered as a target organ for androgens, as are male sex accessory organs, since all events involved in testosterone action have been observed in this tissue. As a corollary, the mechanism of androgen action can be studied in vitro in cultured skin fibroblasts. The advantages of this system are that studies can be performed with intact human cells under carefully controlled conditions, differentiated genetic and biochemical characteristics of the cells are faithfully preserved and the biological material is renewable from a single biopsy specimen. The metabolism of androgens, in particular the 5α-reduction of testosterone to the active metabolite, dihydrotestosterone, the intracellular binding of androgen to its specific receptor protein and its subsequent translocation to the nucleus have been studied in skin fibroblasts. The intracellular androgen receptor content of genital skin fibroblasts is higher than that from nongenital skin sites. In addition, the androgen receptor has been characterized as a specific macromolecule with properties of high affinity and low capacity similar to that of other steroid hormone receptors. The pathophysiology of three genetic mutations which alter normal male sexual development and differentiation has been identified in the human skin fibroblast system. 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. At least two types of X-linked disorders of the androgen receptor exist such that the actions of both testosterone and dihydrotestosterone are impaired and developmental abnormalities may involve both Wolffian derivatives and the external genitalia as well. These two forms of androgen insensitivity result from either the absence of androgen receptor binding activity (receptor(-)form) or apparently normal androgen receptor binding with absence of an appropriate biological response (receptor (+) form). In addition, studies with human skin fibroblasts may also be of value in defining the cellular mechanisms underlying the broad spectrum of partial defects in virilization. In summary, we have correlated our studies of the molecular mechanism of androgen action in human genital skin fibroblasts with those of other investigators as these studies contribute to our understanding of male sexual development and differentiation.

Original languageEnglish (US)
Pages (from-to)3-22
Number of pages20
JournalMolecular and Cellular Biochemistry
Volume36
Issue number1
DOIs
StatePublished - Apr 1981

Fingerprint

Fibroblasts
Androgens
Skin
Androgen Receptors
Dihydrotestosterone
Virilism
Testosterone
Sex Differentiation
Sexual Development
Genitalia
Steroid hormones
Wolffian Ducts
Male Genitalia
Derivatives
Biopsy
Steroid Receptors
Accessories
Metabolites
Macromolecules
Metabolism

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Clinical Biochemistry
  • Cell Biology

Cite this

Cultured human skin fibroblasts : a model for the study of androgen action. / Brown, Terry R.; Migeon, Claude J.

In: Molecular and Cellular Biochemistry, Vol. 36, No. 1, 04.1981, p. 3-22.

Research output: Contribution to journalArticle

Brown, Terry R. ; Migeon, Claude J. / Cultured human skin fibroblasts : a model for the study of androgen action. In: Molecular and Cellular Biochemistry. 1981 ; Vol. 36, No. 1. pp. 3-22.
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