The aims of this research is to enhance our knowledge concerning the role of hormones in the developmental processes during pregnancy. In the first part of the application we describe our effort to date and future plans on the isolation of a fetal pituitary factor which stimulates the formation of C19 and C21 steroids by the fetal adrenal at 19 weeks gestation but only C19 steroids at 15 weeks gestation. In the second part we outline our plans to continue our efforts to isolate a possible corticotropin releasing factor from the adrenal cortex of the fetal calf which stimulated ACTH production from the fetal adrenal. In the third section we describe our plans to isolate peptides from the calf feta pituitary (anterior and neurointermediate lobes) throughout gestation. This will allow us to determine whether some peptides are made in larger amounts and then decrease with time. We have embarked on the isolation of peptides from the fetal lung. Initially we have been extracting the calf fetal lung but we also plan to examine the rabbit fetal lung. We will biosynthesize the peptides using 3H labeled amino acid and identify the fragments formed after tryptic digestion. Initially we are looking for peptides such as CLIP, ACTH1-38, ACTH1-39 and alpha-MSH with which we have a lot of experience and later we will look for others which have been detected or which we find to be biosynthesized as unknowns. In the last part of the application we will test all of the peptides we have isolated in the last two years in our calf fetal adrenals system which synthesizes C19 and C21 steroids and in our rat adrenal cell system. During the last two years this laboratory has developed sensitive methods for the extraction, HPLC separation and identification of peptides. Now we are in the process of applying these methods to important biologic problems. The data which we will obtain will help us understand fetal development as it pertains to the lung directly and indirectly via the fetal adrenal pituitary-axis and will be useful in esigning drugs and methods of treatment against the REspiratory Distress Syndrome. Our next area of development will be the fetal intestine which we may get to during the next three years.
Showing the most recent 10 out of 26 publications
