Use of artificial androgen receptor coactivators to alter myoblast proliferation

Cara Benjamin, Guido Jenster, Jorge A. Piedrahita

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

Skeletal muscle has long been thought to be a target tissue for androgens, eliciting their effect through the androgen receptor. In order to better understand androgen receptor action, a series of mutated androgen receptors were developed and their degree of specificity and cellular responses determined. Specificity, as measured by a reporter assay using HeLa cells, indicated that mutation of the ligand-binding domain or the AR (mutation H865Y), in combination with the p65 transactivating domain, resulted in an increased response to androgens as well as decreased specificity. Transfection of the mutant AR into mouse and rat myoblast cell lines resulted in an increase in expression of the reporter gene consistent with the data from HeLa cells. Overexpression of the wild type or mutant AR into myoblasts and treatment with testosterone induced both greater proliferation and faster differentiation of the cells compared to those expressing endogenous AR. Additionally, when treated with estrogen, these cells were able to proliferate and differentiate to similar levels as cells treated with testosterone. The ability of the mutated AR to act as an artificial coactivator to up-regulate androgen responsive genes is a useful tool for understanding the interaction of androgens and muscle growth.

Original languageEnglish
Pages (from-to)111-119
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume91
Issue number3
DOIs
StatePublished - Jul 1 2004
Externally publishedYes

Fingerprint

Artificial Receptors
Myoblasts
Androgen Receptors
Androgens
HeLa Cells
Muscle
Testosterone
Genes
Cells
Mutation
Reporter Genes
Transfection
Rats
Cell Differentiation
Assays
Estrogens
Skeletal Muscle
Up-Regulation
Tissue
Ligands

Keywords

  • Androgen receptor
  • Coactivators
  • Muscle growth

ASJC Scopus subject areas

  • Biochemistry
  • Endocrinology

Cite this

Use of artificial androgen receptor coactivators to alter myoblast proliferation. / Benjamin, Cara; Jenster, Guido; Piedrahita, Jorge A.

In: Journal of Steroid Biochemistry and Molecular Biology, Vol. 91, No. 3, 01.07.2004, p. 111-119.

Research output: Contribution to journalArticle

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