Da Silva J A, Larbre J P, Spector T D, Perry L A, Scott D L, Willoughby D A
Department of Experimental Pathology, St Bartholomew's Hospital Medical College, London, United Kingdom.
Ann Rheum Dis. 1993 Apr;52(4):285-91. doi: 10.1136/ard.52.4.285.
Rheumatoid arthritis (RA) is a disease which predominantly affects women. Interestingly, low serum androgen levels and clinical improvement with androgen replacement have been reported in male patients. The aetiopathogenic role of sex hormones in arthritis and their potential long term effects on joint destruction and disability remains unclear, however. This study was designed to investigate the potential influence of sex hormones on inflammation induced cartilage degradation in male rodents.
An in vivo model of cotton wrapped cartilage implants was used to assess the effects of androgen, oestradiol, and progesterone on inflammation induced cartilage degradation, and in vitro techniques were used to investigate the direct actions on cartilage metabolism and cytokine production in male animals.
Orchidectomy resulted in accelerated cartilage damage which was reversed by replacement of physiological levels of androgens. Granulomatous tissue from castrated male rodents produced higher amounts of interleukin 1. Sex hormones reduced spontaneous proteoglycan loss in vitro but did not interfere with the effects of interleukin 1 on cultured cartilage.
Androgens appear to protect cartilage from inflammation induced breakdown in male animals. These results support a pathogenic role for hypoandrogenism in rheumatoid arthritis and suggest that long term androgen replacement may help prevent joint damage and disability.
类风湿性关节炎(RA)是一种主要影响女性的疾病。有趣的是,已有报道称男性患者血清雄激素水平较低,且雄激素替代治疗可改善其临床症状。然而,性激素在关节炎中的发病机制作用及其对关节破坏和残疾的潜在长期影响仍不清楚。本研究旨在调查性激素对雄性啮齿动物炎症诱导的软骨降解的潜在影响。
采用棉包裹软骨植入物的体内模型评估雄激素、雌二醇和孕酮对炎症诱导的软骨降解的影响,并采用体外技术研究其对雄性动物软骨代谢和细胞因子产生的直接作用。
去势导致软骨损伤加速,补充生理水平的雄激素可逆转这一现象。去势雄性啮齿动物的肉芽肿组织产生更多的白细胞介素1。性激素在体外可减少蛋白聚糖的自发丢失,但不影响白细胞介素1对培养软骨的作用。
雄激素似乎可保护雄性动物的软骨免受炎症诱导的破坏。这些结果支持低雄激素血症在类风湿性关节炎中的致病作用,并表明长期雄激素替代治疗可能有助于预防关节破坏和残疾。