The long term objectives of our research is the understanding of normal mechanisms and pathologic variation of human fetal development. Our principal aims in this research application is to study the role of pituitary peptides in fetal development using several model systems. We will study pregnancy in the rabbit to determine possible pituitary peptide involvement in changing adrenal synthesis of corticosteroids. Newly isolated pituitary peptides will be tested for their role in stimulating cortisol synthesis in the adrenal either acting alone or in consert with rabbit ACTH. A second model is the fetal calf pituitary and the study of the ontogeny of peptides and the possibility of isolating unknown peptides which control fetal adrenal growth and steroidogenesis. A third system is the study of N-terminal peptides of proopiomelanocortin to determine whether they have an effect on adrenal steroid synthesis and growth. We have isolated GRP18-27 from human fetal lung and are studying its biologic effects in vivo and in vitro. We have also found evidence of ACTH, calcitonin and an inhibitor of ACTH in human, rabbit and calf fetal lung. We will isolate these peptides and study their physiologic functions. We are trying to isolate a peptide from human fetal pituitary that stimulates C19-steroid synthesis by the fetal adrenal. We are trying to get its sequence so that we can establish its role in fetal homostatis. All of the studies cited above relate to a better understanding of diseases of the newborn such as respiratory distress, and interuterine growth retardation.
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