Secretory rhythm of growth hormone regulates sexual differentiation of mouse liver

The secretory pattern of growth hormone (GH) differs between the sexes; in males it is more pulsatile than in females. Experiments were performed to test the hypothesis that differences in the secretory rhythm of GH are responsible for sex-dependent liver functions of mice. Continuous delivery of GH was achieved either by introducing metallothionein-GH fusion genes into the germ line or by implanting minipumps. Pulsatile delivery of GH was mimicked by injection. The effects of these treatments on production of hepatic prolactin/GH receptors, albumin, and major urinary protein (MUP) were monitored. The results suggest that induction of MUP mRNA requires pulsatile occupancy of GH receptors, which is achieved naturally in males or by injection of GH, whereas chronic occupancy of GH receptors is inhibitory. In contrast, induction of prolactin/GH receptors requires chronic stimulation of GH receptors, which is approximated in normal female mice or results from increased GH levels in mice with foreign genes or undergoing infusions from minipumps.