Multiple mechanisms of heterologous β-adrenoceptor regulation in rat uterus

Abstract

Abstract The inhibitory effects of catecholamines on rat myometrium mediated by β-adrenoceptors are modulated by ovarian steroids. Previously reported findings of radioligand binding studies on myometrial membranes have demonstrated changes in the numbers of β-adrenergic binding sites following ovarian steroid treatment. However, these changes were not accompanied by parallel functional changes. In the present study, we have investigated possible mechanisms of heterologous β-adrenoceptor regulation by ovarian steroids. Binding studies were performed on myometrial membrane and cytosolic preparations from rats which had been ovariectomized and subsequently received no hormonal treatment or had been treated with oestradiol, progesterone or combined oestradiol and progesterone. The β-adrenergic antagonist [125I]iodocyanopindolol and the unlabelled competing agonist, isoprenaline, were used in the present studies. Hormonal treatment had no effect on the concentration of β-adrenergic binding sites in the myometrium (i.e. the number of membrane-bound and cytosolic binding sites per mg protein). However, significant changes were found in the total number of binding sites; these were associated with the hormone-induced tissue hypertrophy. In myometrium from ovariectomized-alone rats, approximately 50% of β-adrenergic binding sites were present in the cytosolic fraction. Oestradiol treatment, either on its own or in combination with progesterone, resulted in the translocation of binding sites to the cell membrane. However, in the absence of progesterone only 33% of the membrane-bound binding sites bound the β-adrenergic agonist, isoprenaline, with a high affinity, suggesting that the majority of these membrane-bound binding sites represented non-functional β-adrenoceptors. Progesterone treatment resulted in a doubling in number of the high affinity membrane-bound receptors. As a result of our findings we propose that oestrogen and progesterone act together in regulating β-adrenoceptor function: it is proposed that oestrogens increase the number of β-adrenergic binding sites associated with the cell membrane while progesterone promotes the coupling of these binding sites to their effector mechanisms thus leading to an increase in the number of functional β-adrenoceptors. Journal of Endocrinology (1995) 147, 303–309