Neuroendocrine peptides have been shown to play paramount roles in the regulation of the functions of the anterior pituitary gland and its target organs and thereby modulate growth, metabolism, reproduction and responses to stressors. The chemical and biological characterization of each new neuroendocrine peptide has led to the revelation of additional actions, perhaps reflective of integrative roles, within the central nervous system and periphery. This program project focuses on the structure and function of peptides and their receptors involved in the regulation of corticotropic cells, including Corticotropin Releasing Factor (CRF), activin and Melanin Concentrating Hormone (MCH) and somatotropic cells, including Growth Hormone Releasing Factor (GRF), activin and somatostatin. We will also study select peptides or proteins derived from cDNA or genomic sequences such as the putative peptides NEI and NGE derived from the rat MCH precursor. We will explore the roles of transcription and tissue specific factors including the Cyclic AMP Response Element Binding protein (CREB) and POU-domain gene products which were characterized by Program participants and which may be important intracellular regulators of the development, proliferation and function of pituitary and neuroendocrine peptide producing cells. This multidisciplinary program involves six projects and five cores with three principal aims: 1) The identification by biochemical and/or recombinant DNA techniques of new regulatory peptides and their receptors; 2) The study of the regulation of neuroendocrine gene expression; 3) The investigation of the physiologic and pathophysiologic significance of selected neuroendocrine peptides especially CRF, GRF and new peptides such as mammalian MCH, activin and the CRF binding protein; 4) The design synthesis and pharmacologic evaluation of neuroendocrine peptide analogs of defined secondary structure in order to gain an understanding of the interactions between the peptides and their receptors. Some of these analogs might ultimately be applied to the investigation, diagnosis or management of conditions such as abnormal growth and development, endocrine neoplasia and stress related disorders of the endocrine, immune, hematopoietic and central nervous systems.
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