I will test the hypothesis that the glutathione (GSH) system modulates the formation of prostaglandins in late gestation, and by doing so, participates in events that lead to parturition. GSH is a required substrate in the biosynthesis of prostaglandin E2 (PGE2), a molecule which is critically important in the initiation of the process of parturition. I will establish the ontogeny of the glutathione system in a variety of organs in the ovine fetus, using measurements of glutathione concentration (Tietze assay) and associated enzyme activities which participate in its synthesis and recycling. These neasurements will be correlated with mRNA obtained by RT-PCR, and various hormone levels. To test the importance of GSH in parturition, I will pharmacologically deplete fetal GSH using buthionine sulfoximine (BSO) and identify any effects of this manipulation on the day of spontaneous parturition. Elucidation of the role for glutathione in parturition will eventually lead to a better understanding of the process as well as a better understanding of the mechanism of prematurity after toxicological insult.
| Wood, Charles E; Gridley, Kelly E; Keller-Wood, Maureen (2003) Biological activity of 17beta-estradiol-3-sulfate in ovine fetal plasma and uptake in fetal brain. Endocrinology 144:599-604 |
| Yuste, R; Bonhoeffer, T (2001) Morphological changes in dendritic spines associated with long-term synaptic plasticity. Annu Rev Neurosci 24:1071-89 |
