Abstract
Lactation dictates a co-ordinated adaptation of the maternal metabolism in the whole animal, and the occurrence and timing of these metabolic changes varies between species. The number and coupling efficiency of β-adrenoceptors in liver membranes and intact hepatocytes were compared as between lactating and non-lactating female rats to assess whether or not attenuation of this signalling system could contribute towards the changed pattern of hepatic metabolism during lactation. In view of the contrasting adaptations of hepatic metabolism to lactation in ruminants, the adrenoceptor profiles of sheep liver membranes were also determined. No changes in the number or affinity of hepatic β-adrenoceptors were found in rats or sheep when lactating and non-lactating individuals were compared. Sheep liver was found to have a greater concentration of β-adrenoceptors than rat liver, and a much higher ratio of β : α1 adrenoceptors. Post-receptor responses at two steps distal to cAMP generation were also evaluated in rat hepatocytes in response to the β-adrenoceptor agonist isoprenaline. The sensitivity and responsiveness of cAMP generation in response to isoprenaline were similar in hepatocytes prepared from lactating and non-lactating rats, although the response to saturating concentrations of glucagon was diminished in hepatocytes from lactating rats. The activity ratio of cAMP-dependent protein kinase (A-kinase) similarly showed no difference with respect to both responsiveness and sensitivity to isoprenaline in these two groups of hepatocytes. In contrast, the sensitivity of rat hepatocyte glycogen phosphorylase activity to isoprenaline challenge was greatly diminished during lactation. These results indicate that: (a) lactation has no impact on the hepatic adrenoceptor population of the rat or sheep; (b) the diminished sensitivity of lactating rat liver glycogen phosphorylase to isoprenaline activation appears to arise at a post-receptor level; and (c) hepatic adrenergic mechanisms other than the β-adrenergic signalling pathway may participate in the post-receptor system which counteracts the activation of glycogen phosphorylase.