Regulation of myometrial adrenoreceptors and adrenergic response by sex steroids.
Regulation of myometrial adrenoreceptors and adrenergic response by sex steroids.
复制标题
性类固醇对子宫肌层肾上腺素受体和肾上腺素能反应的调节。
作者：
J. Roberts;P. Insel;A. Goldfien
子宫肌层肾上腺素能反应和受体受激素环境调节。相对于先用雌激素再用孕酮处理的动物，用雌激素处理的兔子宫表现出α-肾上腺素能优势，并且通过[3 H]二氢麦角隐亭结合测定α-肾上腺素能受体数量增加。在用雌激素和孕酮处理的家兔中，β-肾上腺素能反应占主导地位;然而，通过[125 I]碘羟苄基吲哚洛尔结合测定的β-肾上腺素能受体数量在这些动物和用雌激素处理的动物中相似。比较α-肾上腺素能受体和反应子宫雌激素治疗和未治疗的动物表明，雌激素诱导的增加似乎是负责增加α-肾上腺素能敏感性。在用雌激素处理的兔中，去甲肾上腺素的ED 50降低4.5倍，表明敏感性增加。这种去甲肾上腺素效力的增加不能用治疗诱导的α-肾上腺素能受体激动剂亲和力的变化、儿茶酚胺重摄取或收缩敏感性的非特异性增加来解释。受体浓度增加后去甲肾上腺素的效力增强表明存在备用受体。这得到药理学实验的支持，其中减少可用的α-肾上腺素能受体的数量导致去甲肾上腺素的ED 50增加。与α-肾上腺素能优势状态相反，孕酮治疗产生的β-肾上腺素能优势不能仅用肾上腺素能受体的变化来解释。β-肾上腺素能受体数量、β-肾上腺素能受体与α-肾上腺素能受体的比例以及激动剂对α-或β-肾上腺素能受体的亲和力似乎无法解释β-肾上腺素能优势的发展。因此，虽然性类固醇激素对肾上腺素能受体浓度的改变可以用雌激素治疗产生的子宫肌层α-肾上腺素能优势来解释，但受体的改变不能解释雌激素治疗后孕激素治疗产生的β-肾上腺素能优势。
Myometrial adrenergic response and receptors are modulated by the hormonal environment. Uteri from rabbits treated with estrogen demonstrate alpha-adrenergic predominance and have an increased number of alpha-adrenergic receptors, measured by [3H]dihydroergocryptine binding, relative to animals treated with estrogen followed by progesterone. In rabbits treated with estrogen followed by progesterone, beta-adrenergic response predominates; however, the number of beta-adrenergic receptors measured by [125I]iodohydroxybenzylpindolol binding is similar in these animals and in those treated with estrogen. Comparing alpha-adrenergic receptors and response in uteri from estrogen-treated and -untreated animals reveals that an estrogen-induced increase appears to be responsible for the increased alpha-adrenergic sensitivity. The increased sensitivity is manifest by a 4.5-fold decrease in the ED50 for norepinephrine in rabbits treated with estrogen. This increased potency of norepinephrine is not explained by treatment-induced change of agonist affinity for alpha-adrenergic receptors, catecholamine reuptake, or a nonspecific increase in contractile sensitivity. The enhanced potency of norepinephrine secondary to increased receptor concentration suggests the presence of spare receptors. This is supported by pharmacological experiments in which reducing the number of available alpha-adrenergic receptors results in an increase in the ED50 for norepinephrine. In contrast to the alpha-adrenergic predominant state, the beta-adrenergic predominance produced by progesterone treatment cannot be explained solely by changes in adrenergic receptors. Beta-adrenergic receptor number, the ratio of beta- to alpha-adrenergic receptors, and the affinity of agonists for alpha- or beta-adrenergic receptors seem unable to account for the development of beta-adrenergic predominance. Thus, although modification of adrenergic receptor concentration by sex steroids can be explained by the myometrial alpha-adrenergic predominance produced by estrogen treatment, alteration in receptors cannot account for the beta-adrenergic predominance present when progesterone treatment follows estrogen.