Research Project
3485023
The maintenance of corpus luteum vascularization, growth and steroidogenesis in the pregnant rat is a complex process involving pituitary, placental and ovarian hormones. Estradiol, formed in the luteal cell from either endogenous or placental androgen substrates. acts locally to stimulate blood supply, cell hypertrophy and steroidogenesis of the corpus luteum previously exposed to prolactin from either pituitary or placenta. The first aim of this study is to investigate the molecular mechanism by which estradiol affects vascularization and growth of the corpus luteum. We will investigate the possibility that estradiol enhances blood supply to the corpus luteum by increasing the content and mRNA for basic fibroblast growth factor, the luteal angiogenic factor. Whether the requirement for prolactin and estradiol for the optimal growth of the rat corpus luteum reflects interaction of these two hormones on the production and action of insulin-like growth factor-I will be determined. We will examine the possibility that estradiol enhances cholesterol availability for progesterone biosynthesis by increasing the formation of both HMG-CoA reductase, the key enzyme in cholesterol biosynthesis, and Sterol Carrier Protein 2, the molecule responsible for cholesterol transport to the mitochondria. The significance and the role of estrogen induced changes in calcium-calmodulin and calcium- phospholipid-dependent phosphorylation of specific proteins in subcellular fractions will be investigated. Since estradiol biosynthesis by the corpus luteum depends upon placental androgens from mid-pregnancy, we will determine the reason why the placenta does not synthesize androgen early in pregnancy and determine, throughout placental development, the content and mRNA levels of cytochrome P450scc and P45017 alpha, the enzymes responsible for progesterone and androgen biosynthesis. Finally, we will investigate the mechanism by which LH, estradiol and calcium- calmodulin controls placental steroidogenesis in the rat.
