Department of Nutritional Sciences, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Geroscience, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Harold Hamm Diabetes Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Biochemistry and Molecular Biology, Mayo Clinic, Rochester, MN, USA.
Exp Gerontol. 2020 Dec;142:111113. doi: 10.1016/j.exger.2020.111113. Epub 2020 Oct 14.
Menopause is a natural physiological process in older women that is associated with reduced estrogen production and results in increased risk for obesity, diabetes, and osteoporosis. 17α-estradiol (17α-E2) treatment in males, but not females, reverses several metabolic conditions associated with advancing age, highlighting sexually dimorphic actions on age-related pathologies. In this study we sought to determine if 17α-E2 could prevent ovariectomy (OVX)-mediated detriments on adiposity and bone parameters in females. Eight-week-old female C57BL/6J mice were subjected to SHAM or OVX surgery and received dietary 17α-E2 during a six-week intervention period. We observed that 17α-E2 prevented OVX-induced increases in body weight and adiposity. Similarly, uterine weight and luminal cell thickness were decreased by OVX and prevented by 17α-E2 treatment. Interestingly, 17α-E2 prevented OVX-induced declines in tibial metaphysis cancellous bone. And similarly, 17α-E2 improved bone density parameters in both tibia and femur cancellous bone, primarily in OVX mice. In contrast, to the effects on cancellous bone, cortical bone parameters were largely unaffected by OVX or 17α-E2. In the non-weight bearing lumbar vertebrae, OVX reduced trabecular thickness but not spacing, while 17α-E2 increased trabecular thickness and reduced spacing. Despite this, 17α-E2 did improve bone volume/tissue volume in lumbar vertebrae. Overall, we found that 17α-E2 prevented OVX-induced increases in adiposity and changes in bone mass and architecture, with minimal effects in SHAM-operated mice. We also observed that 17α-E2 rescued uterine tissue mass and lining morphology to control levels without inducing hypertrophy, suggesting that 17α-E2 could be considered as an adjunct to traditional hormone replacement therapies.
绝经是老年女性的一种自然生理过程，与雌激素产生减少有关，导致肥胖、糖尿病和骨质疏松症的风险增加。17α-雌二醇（17α-E2）治疗男性，但不治疗女性，可以逆转与年龄增长相关的几种代谢状况，突出了性别二态性对与年龄相关的病理的作用。在这项研究中，我们试图确定 17α-E2 是否可以防止去卵巢（OVX）对雌性肥胖和骨骼参数的影响。八周龄的雌性 C57BL/6J 小鼠接受 SHAM 或 OVX 手术，并在六周的干预期间接受饮食 17α-E2。我们观察到，17α-E2 可防止 OVX 引起的体重和肥胖增加。同样，子宫重量和腔细胞厚度因 OVX 而减少，并通过 17α-E2 治疗得到预防。有趣的是，17α-E2 可防止 OVX 引起的胫骨干骺端松质骨减少。同样，17α-E2 改善了胫骨和股骨松质骨的骨密度参数，主要在 OVX 小鼠中。与松质骨相反，皮质骨参数受 OVX 或 17α-E2 的影响不大。在非承重的腰椎中，OVX 减少了小梁厚度但不减少间距，而 17α-E2 增加了小梁厚度并减少了间距。尽管如此，17α-E2 确实改善了腰椎的骨量/组织量。总的来说，我们发现 17α-E2 可防止 OVX 引起的肥胖增加和骨量和骨结构的变化，对 SHAM 手术的小鼠影响最小。我们还观察到，17α-E2 可将子宫组织质量和衬里形态恢复到对照水平，而不会引起肥大，这表明 17α-E2 可以被视为传统激素替代疗法的辅助手段。
