Opas Evan E, Rutledge Su Jane, Vogel Robert L, Rodan Gideon A, Schmidt Azriel
Merck Research Laboratories, Department of Molecular Endocrinology and Bone Biology, WP26A1000, West Point, PA 19486, USA.
Maturitas. 2004 Aug 20;48(4):463-71. doi: 10.1016/j.maturitas.2003.11.001.
Develop a rat model for the evaluation of estrogenic agents on estrogen deficiency-induced changes in thermoregulation.
OVX rats are impaired in thermoregulation which manifests itself as an elevation in basal tail skin temperature (TST) and are less able to respond to temperature changes than intact rats.
Administration of estrogen subcutaneously to estrogen-depleted rats either as depot formulation, biodegradable pellets, or daily injections, suppressed the increased TST. OVX rats maintained on a diet devoid of phytoestrogens had a higher TST by several degrees than OVX rats fed normal chow, offering greater ability to test estrogenic agents on thermoregulation. Depletion of estrogen in intact rats via chronic administration of leuprolide acetate, a GnRH agonist, also increased TST, which was in turn suppressed by estrogen. In intact rats, tamoxifen exhibited estrogen antagonistic activity elevating TST, while in OVX rats, tamoxifen acted as an agonist by suppressing TST.
OVX rats kept on a diet devoid of phytoestrogens are a sensitive model for estrogen-dependent thermoregulation.
建立一种大鼠模型，用于评估雌激素缺乏引起的体温调节变化的雌激素类药物。
去卵巢大鼠的体温调节受损，表现为基础尾皮温度（TST）升高，与完整大鼠相比，对温度变化的反应能力较弱。
给雌激素缺乏的大鼠皮下注射雌激素，无论是长效制剂、可生物降解微丸还是每日注射，均可抑制升高的TST。以不含植物雌激素的饮食喂养的去卵巢大鼠的TST比喂食正常饲料的去卵巢大鼠高几度，为测试雌激素类药物对体温调节的作用提供了更强的能力。通过长期给予醋酸亮丙瑞林（一种GnRH激动剂）使完整大鼠体内雌激素耗竭，也会使TST升高，而雌激素又可抑制TST升高。在完整大鼠中，他莫昔芬表现出雌激素拮抗活性，使TST升高，而在去卵巢大鼠中，他莫昔芬通过抑制TST发挥激动剂作用。
以不含植物雌激素的饮食喂养的去卵巢大鼠是雌激素依赖性体温调节的敏感模型。
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