Ontogenetic development of mRNA levels and binding sites of hepatic beta-adrenergic receptors in cattle.
Catecholamines regulate glucose metabolism and affect hepatic glucose production mainly through beta2-adrenergic receptors. The hypothesis was tested that gene expression and numbers of hepatic beta-adrenergic receptors in calves are influenced by age. Examined developmental stages included pre-term (P0) and full-term (F0) calves immediately after birth, full-term calves on day 5 of life (F5), and veal calves (VC) at the age of 159 days. Expression of beta1-, beta2-, and beta3-adrenergic receptor mRNA was measured by real-time PCR. Receptor binding was quantified by saturation binding assays using (3H)-CGP-12177 as a ligand. Abundance of mRNA differed among beta-adrenergic subtypes (beta2 > beta1 > beta3; P < 0.01). Beta3-adrenergic receptor mRNA was undetectable in VC. mRNA abundance for beta2-adrenergic receptors was higher (P < 0.05) in VC than P0 and for beta3-adrenergic receptors was higher (P < 0.001) in F5 than P0. Binding studies revealed most binding of (3H)-CGP-12177 to beta2-adrenergic receptors, which were highest in VC (P < 0.001) and higher (P < 0.05) in F5 than P0. Binding sites correlated positively with mRNA levels of beta2-adrenergic receptors (r = 0.67; P < 0.001), with hepatic activities of phosphoenolpyruvate kinase (r = 0.73; P < 0.001) and with pyruvate kinase (r = 0.4; P < 0.05), and with plasma glucose concentrations (r = 0.5; P < 0.01). In conclusion, mRNA of all three beta-adrenergic receptor subtypes were found in liver, with beta2-adrenergic receptors being the dominant subtype. Numbers of beta2-adrenergic receptors increased with age and were mainly regulated at the transcriptional level. Numbers of beta-adrenergic receptors were positively associated with hepatic activities of gluconeogenetic enzymes and with plasma glucose levels, suggesting functional importance.