Lange Christine, Fernandez Jolene, Shim David, Spurr-Michaud Sandra, Tisdale Ann, Gipson Ilene K
Schepens Eye Research Institute and Department of Ophthalmology, Harvard Medical School, 20 Staniford Street, Boston, MA 02114, USA.
Exp Eye Res. 2003 Jul;77(1):59-68. doi: 10.1016/s0014-4835(03)00064-2.
Dry eye syndrome is prevalent in post-menopausal women, and post-menopausal women secrete less mucus in their reproductive tracts. Using a mouse model, the purpose of this study was to determine if estrogen and/or progesterone regulates Muc4 and Muc5AC gene expression in the ocular surface epithelia, as the hormones do in reproductive tract epithelia.
Adult C57BL/6 mice were ovariectomized, and 19 days later, pellets containing estrogen, progesterone, or a combination were inserted subcutaneously. Ocular surface and reproductive tract tissues were harvested following seven days of hormone treatment. A control group consisted of ovariectomized mice that received no hormone treatment. Real-time reverse transcription-polymerase chain reaction was used to determine the tissue expression levels of mucin mRNA of each treatment group relative to the control. Muc4 mRNA expression levels were determined for the reproductive tract, and both Muc4 and Muc5AC expression levels were determined for the ocular surface epithelia. Muc4 and Muc5AC gene expression in ocular surface and Muc4 in reproductive tract epithelia was demonstrated by In Situ hybridization, and Muc4 and Muc5AC protein was demonstrated in the epithelia of animals in the experimental groups.
The mRNA expression levels of Muc4 and Muc5AC and the immunofluorescence localization pattern in the ocular surface epithelia were not significantly different in any hormone treatment group when compared to the control ovariectomized group. By comparison, mice that were administered estrogen had a significant increase of Muc4 mRNA in the reproductive tract epithelia, progesterone given in combination with estrogen antagonized the upregulatory effects of estrogen in the reproductive tract, and the amount of Muc4 mRNA in the reproductive tract of progesterone-treated animals was not different from ovariectomized controls. Immunofluorescence localization of Muc4 in the reproductive tract epithelia of the experimental groups correlated to message levels, with lack of Muc4 protein detected in the control and progesterone groups.
In comparison to reproductive tract epithelia, Muc4 and Muc5AC are not hormonally regulated by estrogen or progesterone in the ocular surface epithelia of mice. These data demonstrate that regulation of epithelial mucin genes is tissue specific.
干眼症在绝经后女性中普遍存在，且绝经后女性生殖道分泌的黏液较少。本研究利用小鼠模型，旨在确定雌激素和/或孕激素是否像在生殖道上皮中那样调节眼表上皮中的Muc4和Muc5AC基因表达。
对成年C57BL/6小鼠进行卵巢切除，19天后，皮下植入含雌激素、孕激素或二者组合的药丸。激素治疗7天后，采集眼表和生殖道组织。对照组为未接受激素治疗的卵巢切除小鼠。采用实时逆转录-聚合酶链反应来确定各治疗组黏蛋白mRNA的组织表达水平相对于对照组的情况。测定生殖道中Muc4 mRNA的表达水平，同时测定眼表上皮中Muc4和Muc5AC的表达水平。通过原位杂交证实眼表中Muc4和Muc5AC基因的表达以及生殖道上皮中Muc4的表达，并且在实验组动物的上皮中证实了Muc4和Muc5AC蛋白的表达。
与未接受激素治疗的卵巢切除对照组相比，任何激素治疗组眼表上皮中Muc4和Muc5AC的mRNA表达水平及免疫荧光定位模式均无显著差异。相比之下，给予雌激素的小鼠生殖道上皮中Muc4 mRNA显著增加，雌激素与孕激素联合给药可拮抗雌激素在生殖道中的上调作用，孕激素治疗动物的生殖道中Muc4 mRNA含量与卵巢切除对照组无差异。实验组生殖道上皮中Muc4的免疫荧光定位与信息水平相关，在对照组和孕激素组中未检测到Muc4蛋白。
与生殖道上皮相比，雌激素或孕激素在小鼠眼表上皮中对Muc4和Muc5AC没有激素调节作用。这些数据表明上皮黏蛋白基因的调节具有组织特异性。
