Expression of insulin-like growth factor binding protein-1 and -2 genes through the perinatal period in the rat.
Insulin-like growth factor binding proteins (IGFBPs) are essential mediators of the bioavailability and biological effects of the IGFs. Liver expression of the rat (r) IGFBP-1 and rIGFBP-2 genes has been characterized between day 16 in utero (16 diu) and 16 days postnatally (+16 dpn). Run-on experiments showed transcriptional activity of the rIGFBP-1 and rIGFBP-2 genes at birth (B) to be 25 and 5 times that at 16 diu, respectively. After B, transcriptional activity of the rIGFBP-1 gene remained high (140% B at +6 dpn), but that of the rIGFBP-2 gene dropped to 70% B by +6 dpn. Northern blot analysis done simultaneously showed rIGFBP-1 messenger RNA (mRNA) levels to increase approximately 50-fold between 16 diu and B, whereas rIGFBP-2 mRNA increased only 5- to 10-fold. rIGFBP-1 mRNA levels decreased after birth, reaching about 20% B by +6 dpn; rIGFBP-2 mRNA, however, remained stable (about 80% B) at least up to +6 dpn. Parallel Western ligand blot and immunoblot analyses of serum rIGFBPs revealed rIGFBP-1 and rIGFBP-2 concentrations to be increased 3- and 2-fold, respectively between 20 diu and B. Maximal expression of rIGFBP-1 was at +1 dpn (220% B), and of rIGFBP-2, at B. Both rIGFBPs then decreased, reaching about 5% B at adulthood. All these data indicate that increased transcriptional activity of the rIGFBP-1 and rIGFBP-2 genes at birth would determine the increased synthesis in the liver and circulating levels of these proteins. In addition, it would seem that post-transcriptional events (reduced half-life of the rIGFBP-1 messenger after birth, translation efficiency of the rIGFBP-2 messenger) modulate transcriptional regulation.
Babajko
S
S
Unité de Recherches sur la Régulation de la Croissance, INSERM U.142, Hôpital Saint-Antoine, Paris, France.
Hardouin
S
S
Segovia
B
B
Groyer
A
A
Binoux
M
M
D000375:Aging / Q000502:physiology; D000818:Animals; D000831:Animals, Newborn; D002352:Carrier Proteins / Q000097:blood / Q000235:genetics*; D005333:Fetus / Q000378:metabolism / Q000502:physiology*; D015870:Gene Expression; D015151:Immunoblotting; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D008099:Liver / Q000196:embryology / Q000502:physiology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013002:Somatomedins / Q000378:metabolism; D014158:Transcription, Genetic
D002352:Carrier Proteins; D018970:Insulin-Like Growth Factor Binding Protein 1; D018971:Insulin-Like Growth Factor Binding Protein 2; D012333:RNA, Messenger; D013002:Somatomedins