The rat placenta secretes both steroids and luteotropin. The studies described in this proposal investigate these capacities. The placenta is of interest since it is a pivotal organ of reproduction. Its function determines the continuation of pregnancy. Adequate function is the very foundation of successful in vitro fertilization or embryo transplantation programs. Furthermore, desired placental failure leads to successful contraception. Expansion of our knowledge of placental function is needed. The first area of study will investigate steroidogenesis both in vivo and in vitro. The in vivo studies are designed to determine the day to day production of placental progesterone and 20Alpha-hydroxy-4-pregen-3-one. Other in vivo studies are designed to measure the influence of the fetus on steroidogenesis. In vitro studies will seek to measure the day by day steroidogenic capacity of the placenta during periods of placental function and relate it to our in vivo studies. Once these data are established, enzymic inhibitors will be employed to identify the biosynthetic pathways in the placenta. The three enzymic inhibitors to be used are: aminoglutethamide phosphate which blocks conversion of cholesterol to pregnenolone, cyanoketone which prevents the conversion of pregnenolone to progesterone, and SU-10603 which blocks 17Alpha hydroxylas and conversion of progesterone toward testosterone. The results will conclusively demonstrate steroid synthesis. The second area of investigation will be to extend our understanding of the luteotropic role of the placenta and will be explored by maintaining pregnancy with steroanalogs after hypohysectomy done as early as Day 5. Because ongoing serum progesterone and testosterone secretion can be measured in samples obtained serially from these animals the onset of placental luteotropin secretion which supports ovarian steroidogenesis will be determined as well as the time the placenta assumes its total luteotropic role in the model. We have recently identified a luteolytic effect of the fetal-placental unit. Thus, these studies are designed to further define the steroidogenic and luteotropic roles of the rat placenta.
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