Adrenergic receptors have been shown to be involved in uterine contractility. alpha-Adrenergic receptors cause uterine contraction, whereas beta-adrenergic receptors induce relaxation. In animals, myometrial alpha-adrenergic receptors are regulated by gonadal steroids. We have identified alpha 1- and alpha 2-adrenergic receptors in myometrial membranes using the newly developed radiolabeled specific antagonists [3H]prazosin and [3H]rauwolscine. This allowed characterization of both receptor subclasses individually and study of them in various physiological and pharmacological conditions in the human, i.e. during different phases of the menstrual cycle, in postmenopausal women, term pregnancy, and during depo-progestin (medroxyprogesterone acetate) therapy. The affinity and number of alpha 1-adrenergic receptors were unchanged in all conditions, whereas the number of alpha 2-adrenergic receptors increased concomitantly with circulating plasma estradiol levels. However, this latter effect was counteracted by progesterone. These results are an example of the heteroregulation of membrane receptors by estrogens and progesterone and throw new light on the regulatory mechanisms involved in uterine contractility in the human.
Both alpha- and beta-adrenergic receptors have been identified in human myometrium by radioligand binding. Both types of receptors mediate uterine contractility: alpha-adrenergic agonists cause uterine contraction, whereas beta-adrenergic agonists induce relaxation. We studied the possible regulatory effects of gonadal steroids on the affinity, concentration, subtype distribution, and linkage to adenylate cyclase of beta-adrenergic receptors in human myometrium removed during different phases of the menstrual cycle, from postmenopausal women and during depo-progestin (medroxyprogesterone acetate) therapy. We identified beta-adrenergic receptors in human myometrial membranes using the radiolabeled antagonist (--)-[3H]-dihydroalprenolol (DHA). The binding of this radioligand was rapid, reversible, of high affinity (KD = 0.71 nM) and stereo-selective. Total beta-receptor concentration was determined by Scatchard analysis of DHA saturation binding and the ratio of receptor subtypes determined by computer-assisted analysis of beta 2 selective antagonist ICI 118 551/DHA competition binding curves. The fraction of receptors functionally coupled to adenylate cyclase was determined by the agonist/N-ethylmaleimide inactivation method. The affinity of DHA and the fraction of receptors undergoing functional coupling was similar under all hormonal conditions. However, whereas the net concentration of beta-receptors was the same in all groups, beta 1-adrenoreceptors could only be detected in myometrial particulate fractions from uteri obtained in the midfollicular phase, indicating the importance of considering adrenoreceptor subtypes as separately regulatable receptors.
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