MOLECULAR &CELLULAR SIGNALING IN REPRODUCTION &AGING

University Of Nebraska Medical Center, Omaha NE

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Abstract

DESCRIPTION: (Adapted from applicant's abstract) 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.