Monoclonal antibodies to growth hormone (GH) prolong liver GH binding and GH-induced IGF-I/IGFBP-3 synthesis.
This time-course study further explored the mechanisms whereby monoclonal antibodies (MAbs) may enhance growth hormone (GH) effects. Hypophysectomized rats were killed 0, 1, 3, 6, 12, 24, and 48 h after a single injection of bovine (b) GH alone or complexed with an anti-bGH MAb. Serum insulin-like growth factor I (IGF-I) concentrations were increased more and for a longer period after MAb-GH complexes (peak at 24 h: 295 +/- 24 ng/ml) than after bGH alone (peak at 12 h: 219 +/- 37 ng/ml; P < 0.01), whereas liver IGF-I mRNA was similar at 12 h in both groups but remained higher at 24 h (by 65%, P < 0.001) and 48 h (by 64%, P < 0.001) in the presence of the MAb. Induction of serum insulin-like growth factor-binding protein (IGFBP)-3 and liver IGFBP-3 mRNA by bGH also was markedly amplified by the MAb (3.6- and 2-fold at 24 h, respectively; P < 0.01). GH receptors (GHR) remained occupied for a longer period after MAb-GH injection (36 +/- 16 and 35 +/- 8% at 6 and 12 h, respectively) compared with bGH alone (0 +/- 28 and -15 +/- 11%), whereas total liver GH-binding sites and GHR mRNA levels were not affected by the MAb. We conclude that MAbs against GH amplify and prolong the serum IGF-I response to GH, which may result from both a prolongation of liver IGF-I synthesis and an enhanced induction of IGFBP-3. These two effects may in turn be the consequences of sustained GH binding to its liver receptors in the presence of MAb.
Beauloye
V
V
Unité de Diabétologie et Nutrition, Belgium.
Muaku
S M
SM
Lause
P
P
Portetelle
D
D
Renaville
R
R
Robert
A R
AR
Ketelslegers
J M
JM
Maiter
D
D
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology*; D002417:Cattle; D005260:Female; D013006:Growth Hormone / Q000276:immunology / Q000378:metabolism* / Q000494:pharmacology*; D007016:Hypophysectomy; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis* / Q000235:genetics; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011986:Receptors, Somatotropin / Q000187:drug effects / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018972:Insulin-Like Growth Factor Binding Protein 3; D012333:RNA, Messenger; D011986:Receptors, Somatotropin; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone