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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
2R01HD018592-07
Application #
3315675
Study Section
Human Embryology and Development Subcommittee 2 (HED)
Project Start
1986-08-01
Project End
1993-04-30
Budget Start
1989-08-01
Budget End
1990-04-30
Support Year
7
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Columbia University (N.Y.)
Department
Type
Schools of Medicine
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10027
Zheng, M; Pintar, J E (1997) Ontogeny of prohormone convertases in rat prenatal development. Ann N Y Acad Sci 814:108-24
Lugo, D I; Pintar, J E (1996) Ontogeny of basal and regulated proopiomelanocortin-derived peptide secretion from fetal and neonatal pituitary intermediate lobe cells: melanotrophs exhibit transient glucocorticoid responses during development. Dev Biol 173:110-8
Lugo, D I; Pintar, J E (1996) Ontogeny of basal and regulated secretion from POMC cells of the developing anterior lobe of the rat pituitary gland. Dev Biol 173:95-109
Fliegner, K H; Kaplan, M P; Wood, T L et al. (1994) Expression of the gene for the neuronal intermediate filament protein alpha-internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. J Comp Neurol 342:161-73
Zheng, M; Streck, R D; Scott, R E et al. (1994) The developmental expression in rat of proteases furin, PC1, PC2, and carboxypeptidase E: implications for early maturation of proteolytic processing capacity. J Neurosci 14:4656-73
Rogler, L E; Pintar, J E (1993) Expression of the P450 side-chain cleavage and adrenodoxin genes begins during early stages of adrenal cortex development. Mol Endocrinol 7:453-61
Scott, R E; Pintar, J E (1993) Developmental regulation of proopiomelanocortin gene expression in the fetal and neonatal rat pituitary. Mol Endocrinol 7:585-96
Kirchgessner, A L; Pintar, J E (1991) Guinea pig pancreatic ganglia: projections, transmitter content, and the type-specific localization of monoamine oxidase. J Comp Neurol 305:613-31
Gershon, M D; Sherman, D L; Pintar, J E (1990) Type-specific localization of monoamine oxidase in the enteric nervous system: relationship to 5-hydroxytryptamine, neuropeptides, and sympathetic nerves. J Comp Neurol 301:191-213
Scott, R E; Autelitano, D J; Lugo, D I et al. (1990) Developmental changes in levels of proopiomelanocortin intron A-containing heterogeneous nuclear RNA and mature messenger RNA in the anterior and neurointermediate lobes of the rat pituitary. Mol Endocrinol 4:812-20

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