Changes in hepatic androgen sensitivity and gene expression during aging

Bandana Chatterjee, Arun K. Roy

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

The hepatic tissue of the male rat exhibits a gradual decline and ultimate loss in androgen responsiveness during in vivo aging. Appearance of the age-associated androgen insensitivity can be delayed by dietary calorie restriction, an effective means for life-span extension. The androgen receptor mRNA is detectable in the liver only in its androgen-responsive state. Pubertal appearance of hepatic androgen sensitivity is remarkably correlated with the concomitant appearance of a cytoplasmic androgen binding (CAB) protein. Androgen resistance during senescence is associated with the loss of hepatic CAB activity as well. We are investigating the molecular basis for the temporal modulation of this hormone sensitivity through studies on the differential expression of two androgen-responsive marker genes. These are the androgen-repressible SMP-2, and the androgen-inducible α2u-globulin. Androgen resistance of hepatocytes during aging results in repression of the α2u-globulin gene, and depression of the SMP-2 gene. The structural organizations for both of these genes have been characterized. The role of nuclear transcription factors (androgen receptor and any other transacting factor(s) which may be involved) in the coordinate regulation of α2u-globulin and SMP-2 during aging and nutritional manipulation is being explored to establish the molecular mechanism of andropause in the liver.

Original languageEnglish (US)
Pages (from-to)437-445
Number of pages9
JournalJournal of Steroid Biochemistry and Molecular Biology
Volume37
Issue number3
DOIs
StatePublished - Nov 20 1990

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Endocrinology
  • Clinical Biochemistry
  • Cell Biology

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