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.
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.
Bick
T
T
Department of Pharmacology, Bruce Rappaport Faculty of Medicine, Technion-Israel Institute of Technology, Haifa.
Hochberg
Z
Z
Amit
T
T
Isaksson
O G
OG
Jansson
J O
JO
D000818:Animals; D002352:Carrier Proteins / Q000097:blood*; D013006:Growth Hormone / Q000008:administration & dosage* / Q000494:pharmacology; D007016:Hypophysectomy; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D015636:Magnesium Chloride / Q000494:pharmacology; D008297:Male; D010507:Periodicity; D051381:Rats; D011919:Rats, Inbred Strains; D011986:Receptors, Somatotropin / Q000378:metabolism*
D002352:Carrier Proteins; D011986:Receptors, Somatotropin; D015636:Magnesium Chloride; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C051815:somatotropin-binding protein