# AGING AND ANDROGEN RECEPTOR GENE REGULATION

> **NIH NIH R01** · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · 1993 · $161,027

## Abstract

During the life-span of the rat, the liver of both male and female
animals goes through three phases of androgen responsiveness, i.e.,
prepubertal ( <40 days) androgen-insensitivity, an androgen responsive
phase of young-adulthood and androgen-insensitivity of senescence ( <750
days).  These age-dependent changes in androgen sensitivity are
correlated with the hepatic expression of the androgen receptor (AR)
mRNA.  Because of such a marked alteration in the expression of AR gene
during the three periods of life, the rat liver offers a unique model for
exploring the molecular mechanism of the temporal regulation of this
gene.  Such an age-dependent regulation of this receptor gene may be
mediated through a programmed alteration of DNA-protein interactions that
are critical for transcription.  This proposal is designed to undertake
a systematic analysis of DNA-protein interactions that are involved in
the regulation of AR gene expression in the liver.  In order to achieve
this goal, the upstream regulatory region of the AR gene will be cloned
and characterized.  Fragments of the cloned gene will be used to identify
specific protein-binding regions by DNase I in vitro foot-printing
analysis.  Age-specific alterations of DNA-binding nuclear factors will
be subsequently characterized by band-shift analysis of labeled
oligonucleotide duplexes corresponding to the foot-print regions of the
AR gene.  Cellular existence of DNA-protein interactions will be
substantiated by in vivo foot-printing of primary heptocytes and DNase
I hypersensitivity analysis of isolated liver nuclei.  Once the age-
specific DNA-protein interactions are characterized, their functional
relevance will be substantiated by transfection assay of the wild type
and appropriate mutant of the AR gene promoters ligated to heterologous
reporter genes.  The biological role of these interactions will be
further authenticated by examining the specific requirements of the
cis/trans interactions for in vitro transcription of promoter-reporter
constructs.  Results of these studies are expected to provide new
knowledge concerning the molecular mechanism of age-dependent changes in
AR gene expression.  Furthermore, receptor dysregulation is one of the
major causes of the age-associated loss of systemic coordination.  These
studies will therefore, make an important contribution toward an overall
understanding of the molecular basis of aging.

## Key facts

- **NIH application ID:** 3122373
- **Project number:** 1R01AG010486-01A1
- **Recipient organization:** UNIVERSITY OF TEXAS HLTH SCIENCE CENTER
- **SAM.gov UEI:** C3KXNLTAAY98
- **Principal Investigator:** ARUN K. ROY
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1993
- **Award amount:** $161,027
- **Award type:** 1
- **Project period:** 1993-01-01 → 1997-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/3122373

## Citation

> US National Institutes of Health, RePORTER application 3122373, AGING AND ANDROGEN RECEPTOR GENE REGULATION (1R01AG010486-01A1). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/3122373. Licensed CC0.

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