During brain development, the actions of steroid hormones can have lasting effects on reproductive physiology and behavior in animals. Abnormal steroid hormone action in the brain during development can result in generalized endocrine disorders, such as adrenal hyperplasia, infertility, or early/precocious puberty; therefore, understanding how steroid hormone action is regulated within the brain is critical in understanding how endocrine disorders occur. Nuclear receptor co-activators are a recently identified class of proteins that interact with intracellular steroid receptors and profoundly alter their transcriptional activity. The contribution of nuclear receptor co-activators to steroid hormone action on brain development has not been previously explored. The current proposal uses the rat as an animal model and focuses on how nuclear receptor co-activators influence steroid hormone action in the developing brain. We will use antisense oligodeoxynucleotides to reduce the expression of particular nuclear receptor co-activators during brain development and investigate the consequences on sexually dimorphic behaviors and on sexually dimorphic brain structures. This project will also investigate how nuclear receptor co-activators may be involved in regulating two distinct phenomena of brain differentiation: masculinization, which is defined as increased male typical behaviors, and defeminization, which is defined as reduced female typical behaviors. We have recently found that particular nuclear receptor co-activators are critically involved in steroid-induced defeminization but not masculinization of the brain. We propose to further explore how nuclear receptor co-activators influence steroid-induced """"""""sexual differentiation"""""""" of the brain, and how they regulate masculinization vs. defeminization of the brain. My long-term career objective is to become an independent scientist within an academic setting and make important contributions to the field of reproductive physiology. It is his career goal to continue the research presented here in a laboratory of his own, compete for research funding, and to train graduate and postdoctoral students.

Agency
National Institute of Health (NIH)
Institute
National Institute of Mental Health (NIMH)
Type
Research Scientist Development Award - Research & Training (K01)
Project #
7K01MH002035-03
Application #
6720131
Study Section
Special Emphasis Panel (ZRG1-IFCN-2 (01))
Program Officer
Desmond, Nancy L
Project Start
2001-08-10
Project End
2006-07-31
Budget Start
2003-03-14
Budget End
2003-07-31
Support Year
3
Fiscal Year
2002
Total Cost
$100,688
Indirect Cost
Name
University of Wisconsin Madison
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
161202122
City
Madison
State
WI
Country
United States
Zip Code
53715