Uterine prostaglandins (PGs) play an essential role in implantation, parturition, luteolysis and maternal recognition of pregnancy. Yet, the factors regulating uterine synthesis of PGs are poorly understood. The objective of the experiments described in this proposal is to characterize the intracellular mechanisms which regulate this synthesis. Oxytocin stimulates synthesis of PGs from uterine tissue. The experiments described have two specific aims. The first is to examine the role of phospholipase C in mediating the stimulatory effect of oxytocin on uterine synthesis of PGs. Subsequent experiments will be conducted to determine how various integral membrane proteins interact to link the oxytocin receptor to the phospholipase C enzyme. This information will provide a starting point from which to study how various hormones and other agents modify the ability of oxytocin to stimulate activity of phospholipase C. The second specific aim is to determine how intracellular second messengers (i.e. cAMP, diacylglycerol, inositol triphosphate, Ca++) regulate uterine synthesis of PGF 2a. Once important second messengers are identified, experiments will be conducted to characterize the specific regulatory proteins which mediate the second messenger effects (i.e. protein kinases, calmodulin) and the targets of their activity (i.e. lipocortin, phospholipase A2, cyclooxygenase). Improvements in our understanding of these mechanisms has the potential for application in obstetrics, contraception and treatment of infertility and in the reproductive management of food producing livestock.
| Burns, P D; Graf, G A; Hayes, S H et al. (1997) Cellular mechanisms by which oxytocin stimulates uterine PGF2 alpha synthesis in bovine endometrium: roles of phospholipases C and A2. Domest Anim Endocrinol 14:181-91 |
| Silvia, W J; Lee, J S; Trammell, D S et al. (1994) Cellular mechanisms mediating the stimulation of ovine endometrial secretion of prostaglandin F2 alpha in response to oxytocin: role of phospholipase C and diacylglycerol. J Endocrinol 141:481-90 |
| Lee, J S; Silvia, W J (1994) Cellular mechanisms mediating the stimulation of ovine endometrial secretion of prostaglandin F2 alpha in response to oxytocin: role of phospholipase A2. J Endocrinol 141:491-6 |
