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

Abstract

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.

Different α₂-Adrenoceptor Densities in the Circular and Longitudinal Layers of Human Near-Term Myometrium as Revealed by [3H]-Idazoxan Binding Studies

“…Indeed, we find twice as many (^-adrenoceptors in the circular than in the longitudinal layers. These overall con centrations of sites are higher than those pre viously reported [6,16,17]. The binding of ligands to a 2-adrenoceptors shows cation de pendency [18], In the rat brain, McLaughlin and Collins [19] have reported higher [3H]-idazoxan binding in Tris-HCl than in physi ological salt solution.…”

“…In the human pregnant uterus, ligand binding techniques have provided evidence for the presence of a 2-adrenoceptors with the use of [3H]-rauwolscine [6]. Recently, idaz-oxan [RX 781094; 2-(2-l,4-benzodioxanyl)-2-imidazoline HC1], a highly selective cuadrenoceptor antagonist [7] has proved to be a particularly useful ligand for identification of a 2-adrenoceptor sites in the central ner vous system [8].…”

Characterization of α₂-Adrenoceptor Subtypes in Pregnant Human Myometrium

“…Pharmacological evidence of postjunctional · 2 -adrenoceptors in pregnant and nonpregnant myometrium has been available for over a decade [16]. · 2 -Adrenoceptors are in humans able to induce smooth muscle contraction in the myometrium [2].…”

Mecanismos endócrinos e moleculares envolvidos na formação do corpo lúteo e na luteólise: revisão de literatura

“…A P 4 causa a "down regulation" na expressão dos genes que regulam os canais dependentes de cálcio, dificultando a entrada deste íon na célula 47 . A P 4 também inibe a síntese de receptores α-adrenérgicos, que quando ativados causam contrações no miométrio 48 , assim a P 4 é capaz de garantir o relaxamento do miométrio durante a gestação.…”