Upregulation of beta 1-adrenergic receptors in ovariectomized rat hearts.
Changes in cardiac myofilament Ca(2+) activation have been demonstrated in ovariectomized rats. The underlying mechanisms responsible for these changes, however, are unknown. Accordingly, we measured both density and binding affinity of cardiac beta(1)-adrenergic receptors in sarcolemmal preparations from 10-week ovariectomized rats, pair-fed ovariectomized rats, and sham-operated control rats. Receptor protein content was also measured by immunoblotting. Deprivation of ovarian sex hormones for 10 weeks induced a significant upregulation of beta(1)-adrenergic receptors without affecting binding affinity. The same magnitude of receptor upregulation was also detected in pair-fed ovariectomized hearts. To determine which hormone is responsible for the observed increase in beta(1)-adrenergic receptor density, various sex hormone supplemental regimens were administered to ovariectomized rats. Subcutaneous injection of estrogen (5 microg/rat), progesterone (1 mg/rat), or estrogen plus progesterone three times a week all effectively prevented the upregulation of the beta(1)-adrenoceptors. Western blot analyses using polyclonal antibody of beta(1)-adrenergic receptors revealed the same pattern of changes in the protein content of the receptors in these various groups of experimental hearts as those obtained from the receptor binding assay. These results suggest a possible direct suppressive effect of ovarian sex hormones on the expression of cardiac beta(1)-adrenergic receptors.
Thawornkaiwong
Ariyaporn
A
Department of Physiology, Faculty of Science, Mahidol University, Rama 6 Road, Bangkok 10400, Thailand.
Preawnim
Surin
S
Wattanapermpool
Jonggonnee
J
D058671:Adrenergic beta-1 Receptor Antagonists; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D004359:Drug Therapy, Combination; D004967:Estrogens / Q000008:administration & dosage / Q000494:pharmacology; D005260:Female; D006321:Heart / Q000187:drug effects; D015151:Immunoblotting; D007279:Injections, Subcutaneous; D009206:Myocardium / Q000378:metabolism*; D009929:Organ Size / Q000187:drug effects; D010052:Ovariectomy; D011374:Progesterone / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018342:Receptors, Adrenergic, beta-1 / Q000378:metabolism*; D012508:Sarcolemma / Q000378:metabolism; D015854:Up-Regulation; D014599:Uterus / Q000187:drug effects
D058671:Adrenergic beta-1 Receptor Antagonists; D004967:Estrogens; D018342:Receptors, Adrenergic, beta-1; D011374:Progesterone