The ontogeny of alpha 1- and beta-adrenergic receptors and their relative stimulation of phosphorylase alpha activity in hepatic tissue from male and female rats were compared. A decrease in beta-adrenergic receptor concentration and 4-(t-butylamino-2-hydroxypropoxy)-[5,7-3H]benzimidazol-2-one HCl affinity for these sites was found in males and females, when data from membranes of 20- to 22-day animals was compared with that from neonates. No subsequent decline in receptor concentration was noted in the female; however, the beta-mediated phosphorylase activation was further diminished by 49-56 days, suggesting maturational changes beyond the receptor-adenylate cyclase system. Although high-affinity beta-adrenergic receptors were documented in membranes from pubertal males, they were not identified on the intact cells, and activation of phosphorylase alpha via the beta-pathway was minimal. This suggests the majority of the beta-receptors are sequestered in cellular sites not accessible to the hydrophilic ligand or epinephrine in the sexually mature male. Ontogeny of the alpha 1-adrenergic receptors was similar in males and females. Gonadectomy of mature males and females did not eliminate the sexual differences in adrenergic response. However, the ovariectomized females developed an enhanced basal and alpha-adrenergic stimulated phosphorylase activity. The rise in cytosolic free calcium in response to epinephrine was increased in the ovariectomized females to values seen in the intact male, whereas the response in the castrate male was depressed. The results suggest the dimorphism in alpha 1- and beta-adrenergic receptor function is determined by factors other than the ambient concentration of sex steroids in the adult.(ABSTRACT TRUNCATED AT 250 WORDS)
High-affinity binding of agonists to beta-adrenergic receptors on intact cells.
