Roles of pulsatility and continuity of growth hormone (GH) administration in the regulation of hepatic GH-receptors, and circulating GH-binding protein and insulin-like growth factor-I

Abstract

GH secretion in the male rat is characterized by regular GH peaks of high amplitude, and their GH receptors and GH-binding protein (BP) are low. Female rats have a more continuous secretion, and their GH receptors and GH-BP are high. To determine how the pattern of GH delivery may affects the physiological responses to the hormone, hypophysectomized male rats were infused with human GH (1.5 U/kg.day) for 5 days through an implanted iv cannula in either a pulsatile manner (for 5 min every 3 h) or continuously. We then measured free and total (after MgCl2 treatment) somatogenic and lactogenic receptors in hepatic cell membranes, and GH-BP and immunoreactive insulin-like growth factor-I (IGF-I) in serum. The concentrations of occupied, but not free, somatogenic and lactogenic binding sites were higher 5 min after a 5-min infusion of human GH than 90 min after the infusion. Consequently, the total levels (free plus ligand binding) of somatogenic and lactogenic receptors were also higher 5 min after a GH pulse than after 90 min. The levels of circulating GH-BP were higher 90 min than 5 min after a GH pulse, and the serum IGF-I levels did not differ between these time points. The concentrations of free and total somatogenic and free lactogenic receptors in the liver, as well as GH-BP and IGF-I in circulation were higher and body weight gain was lower in rats given continuous GH infusion than after pulsatile infusions. It is concluded that the nature of GH-levels profile has a marked influence on the interrelationship of GH, GH receptors, GH-BP, serum IGF-I and growth, whereby the later is stimulated maximally by pulsatile GH-levels, while the receptor and GH-BP are enhanced maximally by continuous levels. The basis for this discrepancy may lay in the competitive power of GH-BP toward GH receptor binding. A pulsatile GH pattern induced cyclicity in the levels of hepatic cell membrane GH receptors and circulating GH-BP. It is suggested that these factors are regulated in a similar way by the plasma GH pattern in pituitary intact rats.