PRENATAL DIFFERENTIATION OF THE PITUITARY GLAND

Anterior and intermediate lobe proopiomenancortin (POMC) producing cells originate from different regions of an apparently homogeneous precursor structure (Rathke's pouch) that experience different cellular and extracellular interactions during early development. In the adult pituitary gland, these two cell POMC populations exhibit differences in the extent of post translational and regulation of transcription and secretion. In this proposal, we will continue to study the differentiation of these two cell POMC populations and also begin to investigate the differentiation of the adrenal cortex. We will determine the prenatal levels of the POMC primary transcript and mature mRNa by using probes spanning intron-exon splice junctions for solution hybridization and will identify POMC primary transcript containing cells with POMC intron-specific probes for in situ hybridization; taken together, these studies will allow us to identify the earliest stages of POMC transcription in the fetal pituitary. We will analyze the forms of processed oligosaccharides associated with the POMC precursor and POMC derived peptides to determine the intracellular site of POMC cleavage in fetal POMC cells. We will investigate the ontogeny of identified components of endocrine secretory granules to determine whether they are present at stages when we have demonstrated regulated release from fetal POMC cells. We will also investigate the ontogeny of gene expression in the fetal adrenal for three enzymes in the steroid synthetic pathway by solution and in situ hybridization in order to gain insight into the process of differentiation in this tissue. Finally, we will continue to characterize additional components of basement membranes and cell surface receptors for extracellular matrix molecules during stages of fetal pituitary development when phenotypic expression in the fetal pituitary is occurring. Taken together, these studies will advance our understanding of differentiation in distinct populations of fetal POMC cells, provide information about the maturation of the pituitary-adrenal axis and will contribute to our long-range goal of determining the basis for selective hormone gene expression in different regions of the pituitary primordium.