# ANDROGEN RECEPTOR REGULATION OF REPRODUCTIVE FUNCTION

> **NIH NIH R37** · UNIV OF NORTH CAROLINA CHAPEL HILL · 1994 · $276,430

## Abstract

The androgen receptor (AR) is a ligand activated transcriptional
regulatory protein that mediates androgen induced male sexual development
and function.  Sequence analysis of AR cDNA confirmed it as one in the
family of steroid hormone receptor transcription factors who share a
structural arrangement of the major functional domains.  The approach of
site directed mutagenesis and transient expression will be used to further
delineate and characterize specific functional domains of the AR protein.
AR phosphorylation sites will be established by mutagenesis of consensus
kinase recognition sequences and by direct phosphoamino acid analysis of
AR protein.  Effects of phosphorylation on AR function will be determined
by coexpression of mutant and wild type AR expression vectors in the
luciferase reporter gene assay using a variety of cell types and promoter
sequences.  The role of phosphorylation in AR activation, hormone binding,
specific DNA binding and gene activation will be determined. Results with
expressed recombinant AR will be corroborated and extended by studies on
endogenous AR in a hormone responsive highly differentiated Leydig cell
tumor cell line, MA10 cells, that contain a high level of AR.  The
essential residues of the AR nuclear targeting signal will be delineated
by testing for the existence of a bipartite nuclear targeting signal that
spans portions of exons C and D encoding the DNA binding and hinge
regions.  Cell factors required for AR nuclear transport will be
investigated using a permeabilized cell system in vitro.  We will further
define the AR N-terminal and hinge region sequences required for
transactivation, and pursue the hypothesis that a leucine zipper motif in
the N-terminal domain is involved in protein/protein interactions that
facilitate transactivation by AR.  The role of phosphoamino acids in
modulating these actions will also be investigated. AR homo- and/or
heterodimerization will be studied with a focus on two proteins that
interact with AR to enhance DNA binding (AR binding proteins l and 2).
The requirement for AR oligomerization in DNA binding and in gene
activation will be determined.  Finally, an in vitro transcription system
will be established in which the molecular requirements for AR initiation
of gene transcription will be investigated.  These studies will be
facilitated by our recent success in high level expression of AR from a
baculovirus vector in the Trichoplusia ni cabbage looper system for AR
isolation.  Studies outlined in this proposal will contribute to the
understanding of molecular mechanisms of androgen regulated gene
transcription.

## Key facts

- **NIH application ID:** 2197382
- **Project number:** 5R37HD016910-13
- **Recipient organization:** UNIV OF NORTH CAROLINA CHAPEL HILL
- **SAM.gov UEI:** D3LHU66KBLD5
- **Principal Investigator:** ELIZABETH M. WILSON
- **Activity code:** R37 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 1994
- **Award amount:** $276,430
- **Award type:** 5
- **Project period:** 1982-08-01 → 1998-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/2197382

## Citation

> US National Institutes of Health, RePORTER application 2197382, ANDROGEN RECEPTOR REGULATION OF REPRODUCTIVE FUNCTION (5R37HD016910-13). Retrieved via MORVS 2026-10-25 from https://api.morvs.ai/grant/nih/2197382. Licensed CC0.

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