Differential regulation of tissue insulin-like growth factor-binding protein (IGFBP)-3, IGF-I and IGF type 1 receptor mRNA levels, and serum IGF-I and IGFBP concentrations by growth hormone and IGF-I.
The aims of this investigation were (1) to examine IGF-binding protein-3 (IGFBP-3) mRNA levels in candidate tissues which might be important sources for blood IGFBP-3 (liver and skin) and in a target tissue for IGF-I action (skeletal muscle), and (2) to examine the effects of a single dose (500 micrograms) of GH or IGF-I on IGFBP-3 message levels in these tissues since temporal responses (4, 8 and 24 h after the single subcutaneous dose of peptide to GH-deficient dwarf rats) would indicate which peptide is the primary modulator of IGFBP-3 synthesis. Circulating IGF-I and IGFBP-3 concentrations were significantly increased (P < 0.05) by IGF-I and GH. GH treatment increased liver IGFBP-3 mRNA levels by 4 h (P < 0.001 over the 24 h) whereas IGF-I had no effect. Similarly, GH, but not IGF-I, increased muscle IGFBP-3 mRNA levels (P < 0.001 for the 24 h study period). However, both IGF-I and GH induced increases in skin IGFBP-3 mRNA abundance throughout the 24 h period (P < 0.001 and P < 0.01 respectively) and skin IGFBP-3 message abundance was greater that in the liver. Liver IGF-I mRNA levels were, as expected, increased after GH and tended to decrease after IGF-I treatment; muscle IGF-I mRNA was increased by GH (P < 0.001) and, interestingly, progressively increased by IGF-I (P < 0.05 for the 24 h period); skin IGF-I mRNA levels were unchanged by both peptides. The IGF-I induced increase in serum IGFBP-3 concentrations in the absence of an increase in hepatic IGFBP-3 mRNA levels and a paucity of liver IGF-I type 1 receptor mRNA imply that other sources of IGFBP-3 protein or synthesis must exist. The response of skin IGFBP-3 mRNA levels to both GH and IGF-I suggests that other cell types, such as fibroblast-derived cells, could be more important than the liver in the regulation of circulating reservoir IGFBP-3 in certain circumstances. In contrast to some current suggestions, the rapid and consistent GH-induced increase in IGFBP-3 message levels in all tissues studied implies that GH might have a direct function in the regulation of IGFBP-3 synthesis.
Lemmey
A B
AB
Department of Cellular Physiology, Babraham Institute, Cambridge, UK.
Glassford
J
J
Flick-Smith
H C
HC
Holly
J M
JM
Pell
J M
JM
D000818:Animals; D001345:Autoradiography; D015153:Blotting, Western; D013006:Growth Hormone / Q000172:deficiency / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis / Q000097:blood / Q000235:genetics*; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D008297:Male; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology*; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000378:metabolism*
D018972:Insulin-Like Growth Factor Binding Protein 3; D009479:Neuropeptides; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; D017526:Receptor, IGF Type 1