Effects of lactation on the regulation of hepatic metabolism in the rat and sheep: adrenergic receptors and cyclic AMP responses

Abstract

The number and coupling efficiency of beta-adrenoceptors in liver membranes and intact hepatocytes of lactating and non-lactating female rats were compared to assess whether or not alterations in this signalling system could contribute towards the changed pattern of hepatic metabolism during lactation. In view of the different adaptations of hepatic metabolism to lactation in ruminants, the adrenergic receptor profile of sheep liver membranes was also determined. Post-receptor responses at two stages 'down-stream' of cyclic AMP generation were also evaluated in rat hepatocytes in response to the beta-adrenergic agonist isoprenaline. No changes in the number of affinity of hepatic beta-adrenoceptors were found in sheep or rats when lactating and non-lactating individuals were compared. Sheep liver was found to have a much greater concentration of beta-adrenoceptors than rat liver, and a much higher ratio of beta:alpha 1. The sensitivity and responsiveness of cyclic AMP 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 cyclic AMP-dependent protein kinase (PK-A) also reacted similarly (in respect of both responsiveness and sensitivity) to isoprenaline in these two groups of hepatocytes. Contrastingly, the sensitivity of rat hepatocyte phosphorylase activity to beta-adrenergic stimulation was greatly diminished during lactation.