Glucocorticoids regulate the ontogenetic transition of adrenergic receptor subtypes in rat liver.
During neonatal development, adrenergic control of hepatic glucose metabolism undergoes a transition from beta-receptor to alpha 1-receptor-mediated dominance coincident with the onset of function of the hypothalamus-pituitary-adrenocortical axis at the conclusion of the third to fourth week postpartum. To determine whether glucocorticoids contribute to this switch, neonatal rats were given 1 mg/kg of dexamethasone on postnatal days 13, 14 and 15 and the adrenergic receptor population examined by radioligand binding techniques. Dexamethasone accelerated the maturational replacement of beta-receptors with the alpha 1-subtype; the loss of beta-receptors was not reversible upon discontinuing treatment. When the glucocorticoid was given earlier, on days 7, 8 and 9, similar effects were obtained, but the suppression of the beta-subtype was only temporary; treatment before parturition (gestational days 17, 18 and 19) failed to suppress beta-receptor binding. These results suggest that, during a critical period, adrenocorticosteroids provide an important signal for the transition of adrenergic control of hepatic function.
Huff
R A
RA
Department of Pharmacology, Duke University Medical Center, Durham, North Carolina 27710.
Seidler
F J
FJ
Slotkin
T A
TA
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology*; D008099:Liver / Q000254:growth & development / Q000378:metabolism*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011942:Receptors, Adrenergic, alpha / Q000145:classification / Q000378:metabolism*; D011943:Receptors, Adrenergic, beta / Q000145:classification / Q000378:metabolism*
D005938:Glucocorticoids; D011942:Receptors, Adrenergic, alpha; D011943:Receptors, Adrenergic, beta