Department of Stomatology, Universidade Federal do Paraná - UFPR, Curitiba, PR, Brazil.
Department of Physiology and Pathology, Universidade Estadual Paulista - UNESP, School of Dentistry at Araraquara, Araraquara, SP, Brazil.
J Periodontol. 2018 Apr;89(4):486-495. doi: 10.1002/JPER.17-0435.
Testosterone replacement enhances cognitive function and musculoskeletal health in postmenopausal women. However, the biological role of testosterone on inflammation and bone metabolism in females is not well understood. Our objective was to measure the impact of androgens and their receptors on periodontal tissues during periodontal repair in female rats.
Seventy female Holtzman rats were divided into seven groups (n = 10/group): negative control; repair control; androgen receptor antagonist (flutamide, 50 mg/kg, every other day); estrogen receptor antagonist (fulvestrant, 1.5 mg/kg/day); testosterone supplementation (durateston, 250 mg/kg, weekly); aromatase inhibitor (anastrozole, 0.2 mg /kg/day); testosterone plus anastrozole. Cotton ligatures were kept for 13 days, when pharmacological treatment was initiated. On day 14, the ligatures were removed. The rats were euthanized on the 17 or the 28 day (n = 5/group/period) for the evaluation of markers related to inflammation and bone. The tissue and serum samples were evaluated using a multiplexed immunoassay for the inflammatory targets. Radiographic and histologic analyses were performed to assess changes in tissues.
Blockage of androgen receptors had little effect on inflammatory cell count, although it tended to increase interleukin (IL)-4, vascular endothelial growth factor (VEGF), and epidermal growth factor (EGF) as well as decrease IL-1β, tumor necrosis factor (TNF)-α, and IL-6. Flutamide also significantly impaired bone repair (P < 0.05) and had greater osteoclast count, although this last difference was not statistically significant. Testosterone supplementation significantly increased the inflammatory cell count, decreased the levels of IL-4, IL-10, IL-1β, IL-6, and TNF-α; and increased VEGF and EGF.
The blockage of androgen receptors significantly impair bone repair in females through mechanisms that are different from those related to estrogen receptors.
睾酮替代疗法可增强绝经后女性的认知功能和骨骼肌肉健康。然而，雄激素及其受体对女性炎症和骨代谢的生物学作用尚不清楚。我们的目的是在雌性大鼠牙周组织修复过程中测量雄激素和其受体对牙周组织的影响。
70 只雌性 Holtzman 大鼠分为 7 组（n=10/组）：阴性对照组；修复对照组；雄激素受体拮抗剂（氟他胺，50mg/kg，隔日一次）；雌激素受体拮抗剂（氟维司群，1.5mg/kg/天）；睾酮补充剂（达特雄酮，250mg/周）；芳香酶抑制剂（阿那曲唑，0.2mg/kg/天）；睾酮加阿那曲唑。用棉线结扎 13 天，然后开始药物治疗。第 14 天，取出结扎线。第 17 天或第 28 天（n=5/组/期）处死大鼠，评估与炎症和骨相关的标志物。采用多重免疫分析法检测组织和血清样本中的炎症标志物。进行放射学和组织学分析以评估组织变化。
阻断雄激素受体对炎症细胞计数影响不大，但有增加白细胞介素（IL）-4、血管内皮生长因子（VEGF）和表皮生长因子（EGF）以及减少白细胞介素（IL）-1β、肿瘤坏死因子（TNF）-α和白细胞介素（IL）-6的趋势。氟他胺还显著损害骨修复（P<0.05），并增加破骨细胞计数，但这一差异无统计学意义。睾酮补充剂显著增加了炎症细胞计数，降低了白细胞介素（IL）-4、IL-10、IL-1β、IL-6 和 TNF-α的水平，增加了 VEGF 和 EGF。
阻断雄激素受体通过与雌激素受体不同的机制显著损害女性的骨修复。
