ROLE OF PLACENTAL LACTOGEN IN FETAL DEVELOPMENT

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Placental lactogen (PL) has direct metabolic and somatotrophic effects in fetal tissues, suggesting that the hormone plays a role in the control of fetal growth. The biological actions of PL in the fetus are medicated through binding to a distinct and unique PL receptor. The overall objective of this proposal is to examine the physiology and regulation of the PL receptor at the cellular and molecular levels. The mRNA for the sheep PL receptor will be characterized using a cDNA probe isolated from a fetal sheep liver cDNA library. The levels of PL receptor mRNA in maternal and fetal sheep tissues will be examined at various stages of pregnancy to determine whether changes in the binding of PL during development result from changes in the expression of the PL receptor mRNA. The regulation of the PL receptor mRNA by nutritional and hormonal factors will be studied in fetal and maternal sheep liver in vivo and in ovine fetal hepatocytes in vitro. These studies should yield new information regarding the physiology of the Pl receptor at the molecular level and may help to clarify the mechanisms by which various hormones and nutrients regulate the expression of the PL receptor in the pregnant ewe and fetal lamb. Because PL has growth-promoting actions in fetal tissues, these studies should also provide insight into the mechanisms controlling fetal growth in normal and pathological pregnancies. In order to conduct studies of the molecular biology of the PL receptor, I have solicited the assistance of experts with extensive experience in molecular endocrinology. In addition, as a major component of the RCDA, I plan a 15 month sabbatical to obtain training in the theory and techniques of molecular biology. An RCDA would provide the time and opportunity to explore this new area of research and would thereby enhance my career as an independent investigator in the field of fetal endocrinology.