The overall hypothesis to be studied is that cell-to-cell signaling events mediated by astrocytic tryrosine kinase receptors of the ErbB family may contribute to the maintenance of normal reproductive function and, conversely, a decline in the signal capacity of these receptors may lead to a disrupted estrous cyclicity during the early stages of female reproductive aging.
Aim 1 will characterize receptor gene expression, and concentrations of phosphorylated receptors ErbB-1, -2, and -4 will be conducted during normal estrous cycles and preceding the early phases of reproductive aging in the female rat.
Aim 2 will examine whether astrocyte-specific controlled disruption of ErbB receptor signal transduction leads to abnormal estrous cyclicity in adult female mice.
Aim 3 will test the hypothesis that the conditional activation of astrocytic ErbB receptor signal transduction may result in the restoration of normal estrous cycles during the early stages of reproductive aging. The use of an astrocyte-specific inducible system will be investigated in transgenic animals that carry a full length cDNA that encodes a specific ErbB receptor.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG018078-01
Application #
2824450
Study Section
Biochemical Endocrinology Study Section (BCE)
Project Start
1999-09-01
Project End
2004-07-31
Budget Start
1999-09-01
Budget End
2000-07-31
Support Year
1
Fiscal Year
1999
Total Cost
Indirect Cost
Name
University of Nebraska Medical Center
Department
Pediatrics
Type
Schools of Medicine
DUNS #
City
Omaha
State
NE
Country
United States
Zip Code
68198