Strain differences in binding properties of estrogen receptors in immature and adult BALB/c and MRL/MP-lpr/lpr mice, a model of systemic lupus erythematosus

Yacoub Y Dhaher , Ben Greenstein , Elizabeth de Fougerolles Nunn , Munther Khamashta , Graham R.V Hughes
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引用次数: 29

Abstract

The aim was to compare binding properties of estrogen receptors in brain, reproductive and immune tissues of immature and adult female BALB/c mice, and in the same tissues of MRL/MP-lpr/lpr mice. The latter strain spontaneously develops an autoimmune disease resembling human systemic lupus erythematosus (lupus; SLE). It is hypothesized that estradiol, through its receptors, mediates the progression of murine SLE. High-speed cytosols were prepared from hypothalamus, spleen, thymus and uterus of both strains, and incubated with the synthetic estrogen 3H-moxestrol (NEN). Scatchard plots were derived from binding isotherms obtained after in vitro incubation. In addition, cervical lymph nodes from MRL mice could be used, but were too small in BALB/c mice. There was a significant increase in the affinity of the binding reaction i.e. a decrease in the apparent molar dissociation constant (Kd), in immune tissues and uterus with maturation in MRL but not BALB/c mice, whose tissues had, overall, a lower affinity for 3H-moxestrol. Receptor concentrations were significantly higher in spleen and cervical lymph nodes of adult compared with immature MRL mice, but the opposite pattern was observed in BALB/c mouse spleen on maturation. These properties of estrogen receptors in MRL mice may underlie estrogen-mediated exacerbation of murine SLE.

系统性红斑狼疮模型BALB/c和MRL/MP-lpr/lpr未成熟和成年小鼠雌激素受体结合特性的菌株差异
目的是比较未成熟和成年雌性BALB/c小鼠以及MRL/MP-lpr/lpr小鼠脑、生殖和免疫组织中雌激素受体的结合特性。后一种毒株会自发发展为一种类似人类系统性红斑狼疮(狼疮;系统性红斑狼疮)。据推测,雌二醇通过其受体介导小鼠SLE的进展。分别从两菌株的下丘脑、脾脏、胸腺和子宫制备高速细胞溶胶,并与合成雌激素3h -莫雌醇(NEN)孵育。Scatchard图是根据体外培养后得到的结合等温线绘制的。此外,可以使用MRL小鼠的颈部淋巴结,但BALB/c小鼠的淋巴结太小。在MRL而非BALB/c小鼠的免疫组织和成熟的子宫中,结合反应的亲和力显著增加,即表观摩尔解离常数(Kd)降低,而BALB/c小鼠的组织总体上对3H-moxestrol的亲和力较低。与未成熟的MRL小鼠相比,成年小鼠脾脏和颈部淋巴结的受体浓度显著升高,而成熟后BALB/c小鼠脾脏的受体浓度则相反。MRL小鼠雌激素受体的这些特性可能是雌激素介导的小鼠SLE恶化的基础。
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