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

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

Producción científica: Articlerevisión exhaustiva

23 Citas (Scopus)

Resumen

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.

Idioma originalEnglish (US)
Páginas (desde-hasta)728-733
Número de páginas6
PublicaciónProceedings of the National Academy of Sciences of the United States of America
Volumen93
N.º2
DOI
EstadoPublished - ene 23 1996

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