Differential Regulation ofα-Adrenergic Receptor Subclasses by Gonadal Steroids in Human Myometrium*

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Abstract
Adrenergic receptors have been shown to be involved in uterine contractility. α-Adrenergic receptors cause uterine contraction, whereas β-adrenergic receptors induce relaxation. In animals, myometrial α-adrenergic receptors are regulated by gonadal steroids. We have identified α1- and α2-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 α1-adrenergic receptors were unchanged in all conditions, whereas the number of α2-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.