The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures

Michael J. McPhaul, Jean Paul Deslypere, Diane R. Allman, Robert D. Gerard

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

Defects in the androgen receptor cause a spectrum of abnormalities in genetic males ranging from phenotypic women with testicular feminization to men with minor defects in fertility and/or virilization. The diagnosis of androgen resistance can be quite cumbersome, including analysis of the family history, karyotyping, endocrine studies, measurement of androgen binding in genital skin fibroblasts, and, in some instances, sequencing of mutant cDNAs. Furthermore, androgen-binding studies may be normal in patients with qualitative receptor abnormalities or mutations in the DNA-binding domain of the receptor. To circumvent these difficulties, we have used a recombinant adenovirus to deliver an androgen-responsive reporter gene (mouse mammary tumor virus-luciferase) to fibroblasts cultured from genital skin from 12 normal controls and from eight individuals with complete testicular feminization. Following incubation with androgen (2 nM mibolerone) for 72 h, luciferase activity in normal fibroblasts increased >10-fold (range 11-200-fold) in a manner that corresponded with the level of androgen receptor detected in ligand-binding assays. By contrast, luciferase activity increased negligibly in fibroblasts from individuals with testicular feminization (average = 1.2-fold increase). This assay permits a direct assessment of endogenous androgen receptor function in cells and should be a powerful aid in the diagnosis of androgen resistance.

Original languageEnglish (US)
Pages (from-to)26063-26066
Number of pages4
JournalJournal of Biological Chemistry
Volume268
Issue number35
StatePublished - Dec 15 1993

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Androgen Receptors
Fibroblasts
Reporter Genes
Cell culture
Adenoviridae
Androgens
Skin
Genes
Androgen-Insensitivity Syndrome
Luciferases
Assays
Mouse mammary tumor virus
Virilism
Karyotyping
Defects
Viruses
Fertility
Tumors
Complementary DNA
Ligands

ASJC Scopus subject areas

  • Biochemistry

Cite this

The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. / McPhaul, Michael J.; Deslypere, Jean Paul; Allman, Diane R.; Gerard, Robert D.

In: Journal of Biological Chemistry, Vol. 268, No. 35, 15.12.1993, p. 26063-26066.

Research output: Contribution to journalArticle

McPhaul, Michael J. ; Deslypere, Jean Paul ; Allman, Diane R. ; Gerard, Robert D. / The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. In: Journal of Biological Chemistry. 1993 ; Vol. 268, No. 35. pp. 26063-26066.
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