Beta2-adrenoceptor desensitization in non-pregnant estrogen-primed rat myometrium involves modulation of oxytocin receptor gene expression.
The nona-peptide oxytocin (OT) induces contraction of the myometrium by interaction with specific plasma membrane associated OT receptors (OTR), whereas stimulation of beta2-adrenoceptors (beta2AR) causes relaxation. Homologous desensitization of the myometrium to both hormones has been described. However, a possible interaction between the two systems has not been investigated. In the present study, long-term in vivo treatment of non-pregnant estrogen-primed rats with isoproterenol decreased maximal relaxation of isolated uterine strips challenged with isoproterenol. Increased EC50 values of similarly treated animals suggest that the coupling between receptor occupancy and contractile response was impaired. Since beta2AR mRNA levels were left unchanged, we conclude that the homologous desensitization to beta2 stimulation is not due to changes in beta2AR gene expression. OT infusion did not alter beta2AR mRNA levels or isoproterenol-induced relaxation of isolated uterine strips. Treatment with OT had no effect on the amount of myometrial OTR mRNA. We have previously found that OT down-regulates OTR in the non-pregnant rat myometrium, but this therefore does not appear to take place at the level of mRNA production. Isoproterenol treatment resulted in a three-fold increase in OTR mRNA. This was accompanied by a 91% rise in OTR binding and an augmented contractile response of isolated uterine strips to OT, suggesting that the increased production of mRNA reflects formation of active receptors. Neither OTR affinity nor EC50 of in vitro strips was affected by isoproterenol treatment. We conclude that stimulation of beta2AR causes heterologous up-regulation of OTR in the non-pregnant estrogen-primed rat myometrium.
Engstrøm
T
T
Department of Internal Medicine and Endocrinology, Herlev Hospital, University of Copenhagen, Denmark.
Bratholm
P
P
Vilhardt
H
H
Christensen
N J
NJ
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D004967:Estrogens / Q000008:administration & dosage*; D005260:Female; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009119:Muscle Contraction; D009215:Myometrium / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D010121:Oxytocin / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D018045:Receptors, Oxytocin / Q000235:genetics*; D014316:Tritium
D058666:Adrenergic beta-2 Receptor Agonists; D000318:Adrenergic beta-Agonists; D004967:Estrogens; D012333:RNA, Messenger; D018343:Receptors, Adrenergic, beta-2; D018045:Receptors, Oxytocin; D014316:Tritium; D010121:Oxytocin; D007545:Isoproterenol