Plasma somatomedin-C in fasted and refed rats: close relationship with changes in liver somatogenic but not lactogenic binding sites

Circulating levels of somatomedins in man and rats are reduced by fasting and restored by refeeding. To determine the mechanisms for these alterations in somatomedin levels, the affinities and binding capacities of 125 I-labelled bovine GH (somatogenic binding sites) and of 125 I-labelled ovine prolactin (lactogenic binding sites) were assessed in liver homogenates from fasted and refed rats. Correlations were made with plasma immunoreactive somatomedin-C (Sm-C) and plasma insulin. During fasting and refeeding there was a close temporal relationship between the fall and the rise of plasma levels of Sm-C and insulin, and the number of hepatic GH binding sites. After fasting for 1 day, plasma Sm-C dropped by 68% and plasma insulin by 76% when compared with values before fasting. At the same time, GH binding capacity was significantly reduced (7·3 ± 2·8 ( s.e.m. ) pmol/liver v . controls, 20·3 ± 2·1 pmol/liver; P < 0·01). Refeeding for 24 h normalized plasma insulin levels and restored GH binding capacity to values before fasting (13·2 ± 2·4 v . 20·3 ± 2·1 pmol/liver; P > 0·05). Plasma Sm-C rose significantly with refeeding and returned to initial values at day 4 of refeeding (0·82 ± 0·10 v . 0·77 ± 0·07 units/ml; P > 0·05). In contrast, changes in prolactin binding sites correlated poorly with changes in plasma Sm-C. There was a modest decline with fasting significant only after 72 h (6·8 ± 0·6 v . 13·9 ± 3·2 pmol/liver; P < 0·05), and refeeding for 24 h did not restore prolactin binding (5·7 ± 1·2 pmol/liver). Since a number of reports suggest that fasting induces a state of tissue insensitivity to GH, our findings suggest that the reduction in hepatic GH binding capacity might be a mechanism for the fasting-induced reduction in Sm-C. The reduction in plasma insulin, which accompanies fasting, might play a permissive role in the intracellular metabolic events involved in Sm-C and GH receptor regulation.