Regulation of beta 1-adrenoceptors by glucocorticoids and thyroid hormones in fetal sheep.
The effects of betamethasone alone or in combination with thyroxine (T4) on ovine fetal beta-adrenoceptors were investigated at the molecular level. Ovine fetuses (126 days gestation; term = 150 days) were treated with a single ultrasound-guided intramuscular injection of 0.5 mg/kg betamethasone, betamethasone + 50 micrograms/kg T4, or saline. Forty-eight h after injection, lambs were delivered by cesarean section and evaluated three h for postnatal adaptation. Myocardial beta-adrenoceptor equilibrium dissociation constant (Kd) and maximal receptor density (Bmax), as assessed by [3H]dihydroalprenolol binding, were not significantly different in drug-treated groups compared to the control group. Northern hybridization and RNase protection assays of myocardial total RNA probed with a sheep beta 1-adrenoceptor riboprobe confirmed no changes in expression at the level of the gene. Levels of beta 1-adrenoceptor mRNA in the lung and brain were also unaffected by the treatments. Because other genes are responsive to glucocorticoids and thyroid hormones at this stage, the absence of up-regulation of beta-adrenoceptor number and steady-state levels of mRNA coding for beta 1-adrenoceptor following fetal corticosteroid and thyroid hormone treatment may indicate a specific, developmentally regulated repressor mechanism.
Tseng
Y T
YT
Department of Pediatrics, UCLA School of Medicine, Harbor-UCLA Medical Center, Torrance 90502, USA.
Tucker
M A
MA
Kashiwai
K T
KT
Waschek
J A
JA
Padbury
J F
JF
D000818:Animals; D000831:Animals, Newborn; D001345:Autoradiography; D001623:Betamethasone / Q000494:pharmacology; D001667:Binding, Competitive; D015152:Blotting, Northern; D005333:Fetus / Q000187:drug effects*; D015870:Gene Expression; D005938:Glucocorticoids / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D018342:Receptors, Adrenergic, beta-1 / Q000187:drug effects*; D012756:Sheep; D013974:Thyroxine / Q000494:pharmacology*
D005938:Glucocorticoids; D012333:RNA, Messenger; D018342:Receptors, Adrenergic, beta-1; D001623:Betamethasone; D013974:Thyroxine