The long-term objective of this grant proposal is to understand the mechanisms which regulate neuroendocrine peptide expression at various levels and to relate this to the regulation of neuroendocrine function. The current studies will examine the adrenal medulla as a model for studying neuroendocrine peptide regulation in tissues that also express """"""""classical"""""""" hormones or transmitters. The adrenal medulla co-stores and co-secretes two classes of putative hormones, opioid peptides derived from proenkephalin and catecholamines. Recent studies have demonstrated that the expression of multiple hormones within the same cell can be differentially regulted in response to changes in the physiological state of the organism. This may be an important mechanism for regulating the functioning of tissues that express multiple hormones. These studies will therefore examine the question of differential regulation of proenkephalin and catecholamines in the adrenal medulla. This will be addressed at the level of mRNA expression using cDNA probes to proenkephalin and to tyrosine hydroxylase, which is the major regulatory enzyme in adrenal catecholamine biosynthesis.
The specific aims of this proposal will be to compare the expression of preproenkephalin abd tyrosine hydroxylase mRNAs with respect to: 1) regulation in response to increased neurogenic stimulation of the adrenal medulla; 2) hormonal regulation; 3) changes with developmental stage. The mechansims of mRNA regulation will also be examined using transcription rate analysis. Proenkephalin expression in the rat adrenal medulla differs significantly from that in the majority of other mammals, including humans. The studies proposed here will therefore be primarily conducted in the hamster, a species in which the expression of adrenal proenkephalin is more typical. The results of these studies should lead to a greater understanding of the functional significance of catecholamine and opioid peptide co-expression in the adrenal medulla as well as provide basic information about the coordinate and/or differential regulation of multiple hormone expression and function.
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