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EDRI Federal Project Inventory:
Transcriptional Regulation of Steroid Gene Networks
- Sponsor Organization: NATIONAL SCIENCE FOUNDATION
- Project Title: TRANSCRIPTIONAL REGULATION OF STEROID GENE NETWORKS
- Project Focus: HUMAN HEALTH EFFECTS
- Description: Steroid hormones control cell function by turning on and turning off
specific sets ofgenes. The genes controlled by testosterone and other
androgenic hormones areandrogen-dependent tissue. To better understand
how androgens control the expressionof specific genes in the rat
ventral prostate, Dr. Miesfeld has developed an in vitro modelsystem
using a novel rat prostate cell line that was isolated during the
course of NSFsupport. One of the paradoxical observations that he has
been studying is how similarsteroid hormones elicit such distinct
cellular responses in vivo given that the steroidreceptor proteins are
capable of binding to the same gene sequences when studied invitro.
He has proposed that prostate cells contain special androgen receptor
"adaptor"proteins which aid in discriminating between androgen action
and that of glucocorticoidswhich bind to a related steroid receptor.
By understanding more about these cell-specificsteroid responses, it
should be possible to uncover the molecular basis of gene-
selectivetranscription. In this proposed research, Dr. Miesfeld
intends to focus his efforts on threespecific aims. First, he will
use two model androgen regulated genes, and either liver cellsor
prostate cells, to map promoter- and cell-specific requirements for
androgen receptorsequences that may interact with putative adaptor
proteins. These proteins may act as"activators" in prostate cells or
as "inhibitors" in liver cells based on earlier observationsthat
androgen receptors function 10-20 times better in prostate cells.
Second, he will useyeast cells to set up a genetic screen to identify
new mutations in the androgen receptorthat affect these promoter- and
cell-specific responses. One prediction from thehypothesis is that
different proteins will interact with the modulatory domain of
theandrogen receptor in distinct ways such that mutations should be
able to distinguishbetween them. Third, he will use biochemical
techniques to physically isolate proteinsfrom prostate cells that
specifically interact with the androgen receptor modulatory domain.
The characterization of these proteins should provide new information
regardingmechanisms of steroid-regulated gene expression.
- References:
- Category: MODELS
- Subcategory: BASIC RESEARCH
- Keywords for Experimental System/Species: RODENT, MAMMAL, IN VIVO, IN VITRO, LABORATORY STUDIES
- Keywords for Experimental Endpoints: REPRODUCTIVE, HORMONE MEASURES, HORMONE RECEPTORS, SEX STEROIDS,
PEPTIDEHORMONES, PHYSIOLOGY, BREEDING BEHAVIOR, MOLECULAR, GENE
EXPRESSION
- Chemical Agents: Sex Steroids
- Performing Institution: University of Arizona
- Contact: Roger L Miesfeld, 601 Administration Bldg, Tucson, AZ 85721 602
621-2211
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