AGE-RELATED RESPONSE OF SALIVARY GLANDS TO ISOPROTERENOL

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It is proposed to utilize salivary glands as an in vivo model for investigating the mechanism(s) regulating the beta-adrenergic- receptor mediated expression of two different genes in the same cell, one which is expressed during normal development (LM) and the other a proto-oncogene (c-fos), the developmental pattern of which is unknown. An increased understanding of the factors regulating the expression of a gene which is expressed during normal development of salivary glands, and a proto-oncogene both of which can be induced to express by the same beta-adrenergic agonist, and the manner in which their expression may be altered is essential for rational approaches toward understanding both normal and aberrant cellular mechanisms. We have recently cloned the cDNA coding for the LM secretory protein and propose to use the clone to examine the following specific aims: I. to determine the developmental pattern of expression of the LM gene and to correlate this expression with indices of differentiation and growth of salivary glands in vivo (both physiologic and stimulated), and II. to determine the number of LM gene(s), to isolate and characterize the LM gene(s), to characterize the LM mRNA, and chromosomally localize the LM gene(s), and III. to examine the mechanism(s) by which a beta-adrenergic agonist precociously induces a gene (LM) which is expressed during normal development, and compare and contrast these mechanisms with those of a proto-oncogene (c-fos) which is not known to be expressed during normal development, but can be induced to express by the same agent. The studies outlined on postnatal development of salivary glands will be the basis of future experiments designed to examine these parameters in aging and senescent animals.