Myometrial beta 1-adrenoreceptors are detectable only in the midfollicular phase

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.