Horwitz K B, Horwitz L D
J Clin Invest. 1982 Apr;69(4):750-8. doi: 10.1172/jci110513.
Sex differences and steroid hormones are known to influence the vascular system as shown by the different incidence of atherosclerosis in men and premenopausal women, or by the increased risk of cardiovascular diseases in women taking birth control pills or men taking estrogens. However, the mechanisms for these effects in vascular tissues are not known. Since steroid actions in target tissues are mediated by receptors, we have looked for cytoplasmic steroid receptor proteins in vascular tissues of dogs. We find specific saturable receptors, sedimenting at 8S on sucrose density gradients for estrogens (measured with [3H]estradiol +/- unlabeled diethylstilbestrol), androgens (measured with [3H]R1881 +/- unlabeled R1881 and triamcinolone acetonide), and glucocorticoids (measured with [3H]dexamethasone +/- unlabeled dexamethasone); they are absent for progesterone (measured with [3H]R5020 +/- unlabeled R5020 and dihydrotestosterone). Progesterone receptors can, however, be induced by 1-wk treatment of dogs with physiological estradiol concentrations (100 pg/ml serum estrogen), indicating a functional estrogen receptor. Receptor levels range from 20 to 2,000 fmol/mg DNA. They are specific for each hormone; unrelated steroids fail to complete for binding. Low dissociation constants, measured by Scatchard analyses, show that binding is of high affinity. Steroid binding sites are in the media and/or adventitia since they persist when the intima is removed. Compared with the arteries, receptor levels are reduced 80% in inferior venae cavae of females, and are absent in the venae cavae of males. We hypothesize that steroid hormones can have direct effects on vascular tissues medicated by specific receptors present in arterial blood vessel walls.
众所周知，性别差异和类固醇激素会影响血管系统，这体现在男性和绝经前女性动脉粥样硬化的发病率不同，或者服用避孕药的女性或服用雌激素的男性患心血管疾病的风险增加。然而，这些作用在血管组织中的机制尚不清楚。由于类固醇在靶组织中的作用是由受体介导的，我们在犬类血管组织中寻找细胞质类固醇受体蛋白。我们发现了特异性可饱和受体，在蔗糖密度梯度上以8S沉降，分别针对雌激素（用[3H]雌二醇±未标记己烯雌酚测量）、雄激素（用[3H]R1881±未标记R1881和曲安奈德测量）和糖皮质激素（用[3H]地塞米松±未标记地塞米松测量）；而孕酮（用[3H]R5020±未标记R5020和双氢睾酮测量）则没有。然而，用生理浓度的雌二醇（血清雌激素100 pg/ml）对犬进行1周治疗可诱导孕酮受体，这表明存在功能性雌激素受体。受体水平范围为20至2000 fmol/mg DNA。它们对每种激素具有特异性；无关的类固醇不能竞争结合。通过Scatchard分析测量的低解离常数表明结合具有高亲和力。类固醇结合位点位于中膜和/或外膜，因为去除内膜后它们仍然存在。与动脉相比，雌性下腔静脉中的受体水平降低了80%，而雄性下腔静脉中则没有受体。我们推测类固醇激素可通过存在于动脉血管壁中的特异性受体对血管组织产生直接影响。
