SEX HORMONE REGULATION OF LACRIMAL GLAND SECRETION

性激素对泪腺分泌的调节

• 批准号: 3266838
• 负责人: DWIGHT W WARREN
• 金额: $ 8.15万
• 依托单位: UNIVERSITY OF SOUTHERN CALIFORNIA
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1994-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3266838
• 关键词: acinar cell; androgens; autocrine; beta adrenergic receptor; bromocriptine; estrogens; female; hormone binding protein; hormone inhibitor; hormone regulation /control mechanism; ion transport; laboratory rabbit; lacrimal apparatus; messenger RNA; muscarinic receptor; northern blottings; ovariectomy; paracrine; peptide hormone biosynthesis; prolactin; secretion; sex hormones; sodium potassium exchanging ATPase; tear; western blottings

DESCRIPTION (adapted from applicant's abstract): Dry eye disease is one of the most frequently encountered categories of ocular morbidity, and insufficient lacrimal gland fluid production is a frequent source of the problem. Lacrimal insufficiency results from autoimmune disease, most notably Sjogren's syndrome, and from other, poorly-understood etiologies. Most dry eye patients, and the vast majority of Sjogren's syndrome patients, are postmenopausal women. Additionally, many women who are pregnant or are taking oral contraceptives are unable to wear contact lenses due to decreased aqueous tear production. Thus, it appears that reproductive hormones modulate lacrimal secretory function and susceptibility to autoimmune disease. The goal of this study is to determine the hormonal factors regulating the secretory status of the female lacrimal gland. The specific aims are to test three hypotheses concerning interactions between androgens, estrogens, and prolactin: 1. Decreasing androgen and increasing estrogen levels result in lacrimal insufficiency. Because androgens as well as estrogens are lost after menopause, and because increasing estrogen levels decrease free androgens by increasing synthesis of sex hormone binding globulin, this hypothesis can account for the observation that lacrimal function is impaired both post-menopausally and in high-estrogen states. 2. Prolactin at optimal levels acts synergistically with androgens and estrogens in maintaining normal lacrimal gland function, while either insufficient or excess prolactin impairs function. 3. Prolactin synthesis in the lacrimal gland is decreased by androgens and circulating prolactin, and it is increased by estrogens. This hypothesis, to be tested with materials from the first two specific aims, is of interest because of the possibility that prolactin might act as an intracrine, or if released into the interstitium, an autocrine or paracrine mediator of lacrimal epithelial or lymphocytic activity. Rabbits will be ovariectomized, then treated with androgens, with and without estrogens, to test the first hypothesis. They will be treated with bromocriptine, prolactin, and sex steroids to test the second. Total membrane-associated Na,K-ATPase, muscarinic receptors, and beta-adrenergic receptors will be measured in initial surveys. The subcellular organization of these parameters, plus Na/H antiport, will be determined in final experiments, as will resting and cholinergically stimulated lacrimal gland fluid flow rates, lacrimal immunohistopathology, and acinar morphology. Prolactin mRNA abundance and immunoreactivity will be measured to test the third hypothesis. If the specific hypotheses are proven correct, the experimental results should inspire design of strategies for preventing or reversing hormonally-mediated lacrimal insufficiency.

描述（改编自申请人的摘要）：干眼病是一种 最常见的眼部疾病类别，以及 泪腺液产生不足是 问题. 泪腺功能不全是由自身免疫性疾病引起的， 尤其是干燥综合征，以及其他病因学知之甚少。 大多数干眼症患者和绝大多数干燥综合征患者 患者为绝经后妇女。 此外，许多女性 怀孕或正在服用口服避孕药者不能戴隐形眼镜 晶状体由于减少水泪液的产生。 因此，似乎 生殖激素调节泪液分泌功能， 自身免疫性疾病的易感性。 本研究的目的是 确定调节分泌状态的激素因素， 女性泪腺 具体目的是检验三个假设 关于雄激素、雌激素和催乳素之间的相互作用：1. 雄激素减少和雌激素水平增加会导致泪腺炎 不足。 因为雄激素和雌激素都会丢失 更年期，因为增加雌激素水平减少游离雄激素 通过增加性激素结合球蛋白的合成， 可以解释泪腺功能受损的观察结果， 绝经后和高雌激素状态。 2. 最佳催乳素 水平与雄激素和雌激素协同作用， 正常的泪腺功能，而无论是不足或过剩 催乳素损害功能。 3. 催乳素在泪腺中的合成 雄激素和循环催乳素降低， 雌激素类。 这一假设，将用前两个材料进行测试， 具体的目的，是感兴趣的，因为催乳素的可能性， 可能作为一种内分泌，或者如果释放到氚中， 泪腺上皮或淋巴细胞的自分泌或旁分泌介质 活动 兔子将被切除卵巢，然后用雄激素治疗， 有没有雌激素，来检验第一个假设 他们将 用溴隐亭催乳素和性类固醇来测试第二种 总膜相关Na，K-ATP酶，毒蕈碱受体，和 将在初步调查中测量β-肾上腺素能受体。 的 这些参数的亚细胞组织，加上Na/H反向转运，将是 在最后的实验中确定，休息和胆碱能 刺激泪腺液流速，泪腺免疫组织病理学， 和腺泡形态。 催乳素mRNA丰度和免疫反应性将 来检验第三个假设。 如果具体的假设是 被证明是正确的，实验结果应该启发设计 预防或逆转尿道介导的泪腺炎的策略 不足。