Opas Evan E, Gentile Michael A, Kimmel Donald B, Rodan Gideon A, Schmidt Azriel
Department of Molecular Endocrinology and Bone Biology, Merck Research Laboratories, West Point, PA 19486, USA.
Maturitas. 2006 Jan 20;53(2):210-6. doi: 10.1016/j.maturitas.2005.04.006.
Estrogen is the most effective treatment for preventing the vasomotor symptoms in women. The ability of estrogen to control tail skin temperature (TST) in rats is used as an animal model for the studies of estrogens on menopausal hot flushes. Today, we know that estrogen can mediate its actions via the interaction with two different estrogen receptors: ERalpha and ERbeta. To elucidate the function of each estrogen receptor subtype control of thermoregulation, we developed an animal model demonstrating estrogen control of TST in mice.
We determined that estrogen depletion by ovariectomy (OVX) of mice causes an elevation of basal tail skin temperature. Administration of estradiol cypionate suppressed this increase in TST in a dose dependent manner. Estrogen depletion by OVX in either ERalpha-knockout (ERalphaKO) or ERbeta-knockout (ERbetaKO) mice resulted in an increase in TST that could be suppressed by estrogen treatment.
We show that mice serve as a suitable animal model for estrogen-controlled thermoregulation and that the expression of either ERalpha or ERbeta alone in mice is sufficient to maintain control TST by estrogen.
雌激素是预防女性血管舒缩症状最有效的治疗方法。雌激素控制大鼠尾部皮肤温度(TST)的能力被用作研究雌激素对更年期潮热作用的动物模型。如今,我们知道雌激素可通过与两种不同的雌激素受体:雌激素受体α(ERα)和雌激素受体β(ERβ)相互作用来介导其作用。为阐明每种雌激素受体亚型对体温调节的控制功能,我们建立了一种动物模型,以证明雌激素对小鼠TST的控制作用。
我们确定,通过切除小鼠卵巢(OVX)使雌激素缺乏会导致基础尾部皮肤温度升高。给予环丙孕酮抑制TST的这种升高呈剂量依赖性。在雌激素受体α基因敲除(ERαKO)或雌激素受体β基因敲除(ERβKO)小鼠中,通过OVX使雌激素缺乏导致TST升高,而雌激素治疗可抑制这种升高。
我们表明,小鼠是雌激素控制体温调节的合适动物模型,并且小鼠中单独表达ERα或ERβ足以维持雌激素对TST的控制。