The biologic changes that occur following menopause have heightened interests in the relationship between declining plasma estrogen levels and health in this aging female population. Specifically, in postmenopausal women, the development of atropic oral epithelial cells, which are easily stripped from the underlying connective tissue, hinders proper oral hygiene and impairs the prescribed utilization of dental prostheses. The broad aims of this research are 1) to understand the actions of estrogens on oral tissues and 2) to elucidate the relationship(s) between extracellular matrix proteins secreted by fibroblasts from young versus senescent gingiva, and the effects of such proteins on normal and aberrant epithelial cell growth. As a model system, human fibroblasts derived from the gingiva of premenopausal, postmenopausal and affected postmenopausal females (i.e., those with gingiva exhibiting a hormone-induced desquamative lesion) will be used to define estrogen action in the gingiva. This proposal will examine estrogen effects on proliferation, glycosaminoglycan synthesis, collagen synthesis, noncollagen protein synthesis and collagen expression in fibroblasts from both young and elderly females. Experiments will be performed to determine if maintenance of estrogen sensitivity is a characteristic of the premenopausal fibroblast secretory phenotype and whether it is lost in fibroblasts of elderly individuals with hormone- induced desquamative lesions. Further experiments will analyze cytosol and nuclear estrophiles as well as estrogen metabolism, to determine the mechanism by which estrogen sensitivity is lost. Finally a study of epithelial growth will be examined by in vitro cultivation of epithelial cells on estrogen-stimulated extracellular matrix proteins secreted by gingival fibroblasts, to determine if gingival epithelial cell proliferation, attachment, and keratin proteins are dependent on extracellular matrices secreted by estrogen-stimulated fibroblasts. Knowledge gained from the proposed research on gingival fibroblast and epithelial cell function in young and elderly females, as ell as a new understanding of how these cells respond in the presence of estrogens, should provide the rational for the development of novel therapeutic approaches in the control of hormone-induced oral and other mucosal desquamations.
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