Green P G, Dahlqvist S R, Isenberg W M, Strausbaugh H J, Miao F J, Levine J D
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, California 94143-0440, USA.
J Neurosci. 1999 May 15;19(10):4082-9. doi: 10.1523/JNEUROSCI.19-10-04082.1999.
To investigate the role of sex steroids in sex differences in the response of rats to the potent inflammatory mediator bradykinin (BK), we evaluated the effect of sex steroid manipulation on the magnitude of BK-induced synovial plasma extravasation (PE). The magnitude of BK-induced PE is markedly less in females. Ovariectomy of female rats increased BK-induced PE, and administration of 17beta-estradiol to ovariectomized female rats reconstituted the female phenotype. Castration in male rats decreased BK-induced PE, and administration of testosterone or its nonmetabolizable analog dihydrotestosterone reconstituted the male phenotype. The results of these experiments strongly support the role of both male and female sex steroids in sex differences in the inflammatory response. Because the stress axes are sexually dimorphic and are important in the regulation of the inflammatory response, we evaluated the contribution of the hypothalamic-pituitary-adrenal and the sympathoadrenal axes to sex differences in BK-induced PE. Neither hypophysectomy nor inhibition of corticosteroid synthesis affected BK-induced PE in female or male rats. Adrenal denervation in females produced the same magnitude increase in BK-induced PE as adrenalectomy or ovariectomy, suggesting that the adrenal medullary factor(s) in females may account for the female sex steroid effect on BK-induced PE. Furthermore, we have demonstrated that in female but not male rats, estrogen receptor alpha immunoreactivity is present on medullary but not cortical cells in the adrenal gland. These data suggest that regulation of the inflammatory response by female sex steroids is strongly dependent on the sympathoadrenal axis, possibly by its action on estrogen receptors on adrenal medullary cells.
为了研究性类固醇在大鼠对强效炎症介质缓激肽（BK）反应的性别差异中的作用，我们评估了性类固醇操作对BK诱导的滑膜血浆外渗（PE）程度的影响。BK诱导的PE程度在雌性大鼠中明显较低。雌性大鼠卵巢切除增加了BK诱导的PE，而给卵巢切除的雌性大鼠施用17β-雌二醇可恢复雌性表型。雄性大鼠去势降低了BK诱导的PE，而施用睾酮或其不可代谢的类似物二氢睾酮可恢复雄性表型。这些实验结果有力地支持了雄性和雌性性类固醇在炎症反应性别差异中的作用。由于应激轴具有性别差异且在炎症反应调节中很重要，我们评估了下丘脑-垂体-肾上腺轴和交感肾上腺轴对BK诱导的PE性别差异的贡献。垂体切除或皮质类固醇合成抑制均未影响雌性或雄性大鼠中BK诱导的PE。雌性大鼠肾上腺去神经导致BK诱导的PE增加幅度与肾上腺切除或卵巢切除相同，这表明雌性大鼠中的肾上腺髓质因子可能解释了雌性性类固醇对BK诱导的PE的影响。此外，我们已经证明，在雌性而非雄性大鼠中，肾上腺髓质而非皮质细胞上存在雌激素受体α免疫反应性。这些数据表明，雌性性类固醇对炎症反应的调节强烈依赖于交感肾上腺轴，可能是通过其对肾上腺髓质细胞上雌激素受体的作用。
