Molecular Pharmacology, Vol 20, 52-58, Copyright © 1981 by the American Society for Pharmacology and Experimental Therapeutics

Regulation of Myometrial Adrenoreceptors and Adrenergic Response by Sex Steroids

¹ Department of Obstetrics, Gynecology and Reproductive Sciences, Medicine and Cardiovascular Research Institute, University of California at San Francisco, San Francisco, California 94143, and University of California at San Diego, San Diego, California 92093

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.

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