SEX HORMONE REGULATION OF LACRIMAL GLAND SECRETION

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Dry eye disease, including Sjogren's syndrome, is one of the most frequently encountered categories of ocular morbidity. The etiology of this problem appears to result from two pathologic alterations in function. The first is autoimmune disease, most notably Sjogren's syndrome. The second is non-autoimmune lacrimal dysfunction, which appears to be hormonally mediated. Most patients presenting with dry eye problems, and the vast majority with Sjogren's syndrome (>90%), are postmenopausal women. Additionally, many women who are pregnant or taking oral contraceptives are unable to wear contact lenses due to decreased aqueous tear production. The long term objectives of this proposal are to determine the hormonal factors involved in regulating secretion by the female lacrimal gland. In order to determine hormonal control mechanisms of lacrimal gland secretion in the female, specific aims have been developed to test the following hypotheses: 1. Critical levels of androgens are essential to maintain lacrimal gland function. 2. Prolactin at optimal levels acts synergistically with androgens in maintaining normal function, while either insufficient or excess prolactin impairs lacrimal function. 3. Prolactin synthesis in the lacrimal gland is decreased by androgens and circulating prolactin. Rabbits will be used in this proposal. They will be ovariectomized and then treated with the various hormones. Resting and cholinergically stimulated Iacrimal gland fluid flow rates will be measured in vivo. Protein, DNA, Na,K-ATPase, and neurotransmitter receptor ligand binding activities will be measured after subcellular fractionation. The abundances of mRNA for the various receptors will be quantified in lacrimal gland extracts. Prolactin mRNA and prolactin will be quantified in lacrimal glands in appropriate experiments. Determination of the effects of each hormone on the multiple signal-transducing and effector systems of lacrimal gland secretion will then allow an understanding of how this organ is coordinately regulated. This information will then lead to development of treatment regimens for hormonally-mediated lacrimal insufficiency.