SEX HORMONE REGULATION OF LACRIMAL GLAND SECRETION

干眼症，包括干燥综合征，是最常见的疾病之一。 常见的眼部疾病类别。 的病因 这个问题似乎是由两种病理改变引起的， 功能 第一种是自身免疫性疾病，最著名的是干燥综合症 综合征 第二种是非自身免疫性泪液功能障碍， 似乎是由尿道介导的 大多数患者表现为干眼症 问题，绝大多数干燥综合征（>90%）， 绝经后妇女。 此外，许多怀孕或服用 口服避孕药是不能戴隐形眼镜，由于减少 泪液分泌 这项建议的长远目标是 确定参与调节分泌的激素因素， 女性泪腺 为了确定荷尔蒙控制机制 在女性泪腺分泌，具体的目标已经 为检验以下假设而开发： 1.关键水平的雄激素是必不可少的，以维持泪腺 功能 2.最佳水平的催乳素与雄激素协同作用， 维持正常功能，而无论是不足或过量催乳素 损害泪液功能。 3.催乳素在泪腺中的合成被雄激素减少， 循环催乳素 本提案将使用兔子。他们将被切除卵巢， 然后用各种激素治疗。 静息和胆碱能 将在体内测量刺激的泪腺流体流速。 蛋白质、DNA、Na，K-ATP酶和神经递质受体配体结合 在亚细胞分级分离后测量活性。 的 各种受体的mRNA丰度将在 泪腺提取物 将对催乳素mRNA和催乳素进行定量 在泪腺中的作用。 测定 每种激素对多种信号转导和效应物的影响 泪腺分泌系统，然后将允许了解 这个器官是如何协调调节的 这些信息将导致 涉及尿道介导的泪腺炎的治疗方案的开发， 不足

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.