Sahlgrenska Osteoporosis Centre, Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Sahlgrenska Academy at the University of Gothenburg, Gothenburg, 413 45, Sweden.
Institute of Biomedicine, Research Centre for Integrative Physiology and Pharmacology, Turku Center for Disease Modeling, University of Turku, Turku, Kiinamyllynkatu 10, FI-20520, Finland.
F1000Res. 2021 Aug 16;10:809. doi: 10.12688/f1000research.54501.1. eCollection 2021.
Estrogens are important regulators of body physiology and have major effects on metabolism, bone, the immune- and central nervous systems. The specific mechanisms underlying the effects of estrogens on various cells, tissues and organs are unclear and mouse models constitute a powerful experimental tool to define the physiological and pathological properties of estrogens. Menopause can be mimicked in animal models by surgical removal of the ovaries and replacement therapy with 17β-estradiol in ovariectomized (OVX) mice is a common technique used to determine specific effects of the hormone. However, these studies are complicated by the non-monotonic dose-response of estradiol, when given as therapy. Increased knowledge of how to distribute estradiol in terms of solvent, dose, and administration frequency, is required in order to accurately mimic physiological conditions in studies where estradiol treatment is performed. In this study, mice were OVX and treated with physiological doses of 17β-estradiol-3-benzoate (E2) dissolved in miglyol or PBS. Subcutaneous injections were performed every 4 days to resemble the estrus cycle in mice. Results show that OVX induces an osteoporotic phenotype, fat accumulation and impairment of the locomotor ability, as expected. Pulsed administration of physiological doses of E2 dissolved in miglyol rescues the phenotypes induced by OVX. However, when E2 is dissolved in PBS the effects are less pronounced, possibly due to rapid wash out of the steroid.
雌激素是调节身体生理机能的重要物质，对代谢、骨骼、免疫系统和中枢神经系统都有重要影响。雌激素对各种细胞、组织和器官产生作用的具体机制尚不清楚，而小鼠模型则构成了定义雌激素生理和病理特性的强大实验工具。通过手术切除卵巢可以在动物模型中模拟绝经，而在去卵巢（OVX）小鼠中用 17β-雌二醇进行替代治疗是一种常用的技术，用于确定激素的特定作用。然而，由于雌二醇治疗的剂量反应是非单调的，这些研究变得复杂。为了在进行雌二醇治疗的研究中准确模拟生理条件，需要了解如何根据溶剂、剂量和给药频率来分配雌二醇。在这项研究中，OVX 小鼠用溶于 Miglyol 或 PBS 的生理剂量 17β-雌二醇-3-苯甲酸酯（E2）进行治疗。每隔 4 天进行皮下注射，以模拟小鼠的发情周期。结果表明，OVX 诱导出骨质疏松表型、脂肪堆积和运动能力受损，这是预期的结果。溶于 Miglyol 的生理剂量 E2 的脉冲式给药可挽救 OVX 诱导的表型。然而，当 E2 溶解在 PBS 中时，效果不那么明显，可能是由于类固醇迅速洗脱。
