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The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. Stimulation of Gs and inhibition of G(o).
J Biol Chem. 1993 Dec 15; 268(35):26063-6.JB

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.

Authors+Show Affiliations

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas 75235-8857.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8253718

Citation

McPhaul, M J., et al. "The Adenovirus-mediated Delivery of a Reporter Gene Permits the Assessment of Androgen Receptor Function in Genital Skin Fibroblast Cultures. Stimulation of Gs and Inhibition of G(o)." The Journal of Biological Chemistry, vol. 268, no. 35, 1993, pp. 26063-6.
McPhaul MJ, Deslypere JP, Allman DR, et al. The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. Stimulation of Gs and inhibition of G(o). J Biol Chem. 1993;268(35):26063-6.
McPhaul, M. J., Deslypere, J. P., Allman, D. R., & Gerard, R. D. (1993). The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. Stimulation of Gs and inhibition of G(o). The Journal of Biological Chemistry, 268(35), 26063-6.
McPhaul MJ, et al. The Adenovirus-mediated Delivery of a Reporter Gene Permits the Assessment of Androgen Receptor Function in Genital Skin Fibroblast Cultures. Stimulation of Gs and Inhibition of G(o). J Biol Chem. 1993 Dec 15;268(35):26063-6. PubMed PMID: 8253718.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The adenovirus-mediated delivery of a reporter gene permits the assessment of androgen receptor function in genital skin fibroblast cultures. Stimulation of Gs and inhibition of G(o). AU - McPhaul,M J, AU - Deslypere,J P, AU - Allman,D R, AU - Gerard,R D, PY - 1993/12/15/pubmed PY - 1993/12/15/medline PY - 1993/12/15/entrez SP - 26063 EP - 6 JF - The Journal of biological chemistry JO - J. Biol. Chem. VL - 268 IS - 35 N2 - 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. SN - 0021-9258 UR - https://www.unboundmedicine.com/medline/citation/8253718/The_adenovirus_mediated_delivery_of_a_reporter_gene_permits_the_assessment_of_androgen_receptor_function_in_genital_skin_fibroblast_cultures__Stimulation_of_Gs_and_inhibition_of_G_o__ L2 - http://www.jbc.org/cgi/pmidlookup?view=long&pmid=8253718 DB - PRIME DP - Unbound Medicine ER -