Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice

Bandana Chatterjee, Chung-seog Song, Myeong H. Jung, Shuo Chen, Christi A Walter, Damon C. Herbert, Frank J. Weaker, Michael A. Mancini, Arun K. Roy

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

The rodent liver displays marked age- and sex-dependent changes in androgen sensitivity due to the sexually dimorphic and temporally programmed expression of the androgen receptor (AR) gene. We have altered this normal phenotype by constitutive overexpression of the rat AR transgene in the mouse liver by targeting it via the human phenylalanine hydroxylase (hPAH) gene promoter. These transgenic animals in their heterozygous state produce an ≃30-fold higher level of the AR in the liver as compared with the nontransgenic control. Androgen inactivation via sulfonation of the hormone by dehydroepiandrosterone sulfotransferase (DST), an androgen-repressible enzyme, also contributes to the age- and sex-dependent regulation of hepatic androgen sensitivity. DST has a broad range of substrate specificity and is responsible for the age- and sex-specific activation of certain polycyclic aromatic hepatocarcinogens as well, by converting them to electrophilic sulfonated derivatives. In the transgenic female, the hepatic expression of DST was ≃4-fold lower than in normal females, a level comparable to that in normal males. The hPAH-AR mice will serve as a valuable model for studying the sex- and age-invariant expression of liver-specific genes, particularly those involved in the activation of environmental hepatocarcinogens such as the aromatic hydrocarbons.

Original languageEnglish (US)
Pages (from-to)728-733
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume93
Issue number2
DOIs
StatePublished - Jan 23 1996

Fingerprint

Androgen Receptors
Transgenic Mice
Androgens
Liver
Phenylalanine Hydroxylase
Genes
Safe Sex
Aromatic Hydrocarbons
Genetically Modified Animals
Substrate Specificity
Transgenes
Rodentia
Hormones
Phenotype
Enzymes
dehydroepiandrosterone sulfotransferase

Keywords

  • aging
  • dehydroepiandrosterone sulfotransferase
  • hepatocarcinogen activation
  • steroid receptor

ASJC Scopus subject areas

  • Genetics
  • General

Cite this

Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice. / Chatterjee, Bandana; Song, Chung-seog; Jung, Myeong H.; Chen, Shuo; Walter, Christi A; Herbert, Damon C.; Weaker, Frank J.; Mancini, Michael A.; Roy, Arun K.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 93, No. 2, 23.01.1996, p. 728-733.

Research output: Contribution to journalArticle

Chatterjee, Bandana ; Song, Chung-seog ; Jung, Myeong H. ; Chen, Shuo ; Walter, Christi A ; Herbert, Damon C. ; Weaker, Frank J. ; Mancini, Michael A. ; Roy, Arun K. / Targeted overexpression of androgen receptor with a liver-specific promoter in transgenic mice. In: Proceedings of the National Academy of Sciences of the United States of America. 1996 ; Vol. 93, No. 2. pp. 728-733.
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