The interrelationship of growth hormone (GH), liver membrane GH receptor, serum GH-binding protein activity, and insulin-like growth factor I in the male rat.
Indirect evidence suggests that the serum GH-binding protein (GH-BP) is related and possibly derived from the GH-receptor. GH, through its specific receptor, is the major regulator of insulin-like growth factor I (IGF-I) synthesis. The present study was undertaken to correlate serum GH-BP activity with liver plasma membrane GH receptors and their effects on serum IGF-I concentration during spontaneous pulsation of rat (r)GH in the normal male rat and after continuous delivery of human (h)GH to hypophysectomized male rats. In the first set of experiments, 45-day-old male rats were decapitated at 15 min intervals for 4 h. Serum GH-BP levels fluctuated with a 60 min lag behind the rGH levels. IGF-I pulsated over a 3-fold concentration range. IGF-I peak levels coincided with one of the rGH peaks, but its periodicity was longer than 3 h. Taken together with our previous studies on the turnover of the GH receptors, we suggest that each GH surge results in individual pulse-related turnover wave of receptor internalization and recycling. This is accompanied by a parallel increase in serum GH-BP activity. The GH and the receptor wave are responsible for an individual secretion pulse of IGF-I. In the second set of experiments male rats were hypophysectomized at 35 days of age. Four days later osmotic minipumps were implanted for continuous delivery of hGH. After 6 days of hGH treatment the rats were killed, blood was collected for hGH, GH-BP, and IGF-I determination, and the livers were removed. Plasma membranes were prepared, and lactogenic and somatogenic binding of [125I]hGH was evaluated. Removal of endogenous ligand was performed by exposing the membranes to 3 M MgCl2. Continuous administration of hGH induced a dose-dependent increase in liver membrane lactogenic and somatogenic binding. Parallel to that increase, serum GH-BP also increased in a dose-dependent manner, and the correlation between serum GH-BP and the liver membrane receptor was significant. Furthermore, hGH induced a dose-dependent increase in IGF-I concentration. There was a close correlation between IGF-I concentration and liver somatogenic receptors. It is concluded that up-regulation of the liver membrane GH receptors is accompanied by increased GH-BP and IGF-I. In both the pulsation experiment and the continuous infusion experiment, GH-BP closely correlated with the liver membrane GH receptor.
Bick
T
T
Rapapaport Family Institute for Research in the Medical Sciences, Haifa, Israel.
Amit
T
T
Barkey
R J
RJ
Hertz
P
P
Youdim
M B
MB
Hochberg
Z
Z
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D013006:Growth Hormone / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008566:Membranes / Q000378:metabolism; D009994:Osmolar Concentration; D011673:Pulsatile Flow; D051381:Rats; D011919:Rats, Inbred Strains; D011979:Receptors, Pituitary Hormone / Q000502:physiology*; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D011979:Receptors, Pituitary Hormone; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone