Multiple mechanisms of heterologous beta-adrenoceptor regulation in rat uterus

The inhibitory effects of catecholamines on rat myometrium mediated by beta-adrenoceptors are modulated by ovarian steroids. Previously reported findings of radioligand binding studies on myometrial membranes have demonstrated changes in the numbers of beta-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 beta-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 beta-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 beta-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 beta-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 beta-adrenergic agonist, isoprenaline, with a high affinity, suggesting that the majority of these membrane-bound binding sites represented non-functional beta-adrenoceptors.(ABSTRACT TRUNCATED AT 250 WORDS)