The effects of dexamethasone treatment on immunoreactive and bioactive insulin-like growth factors (IGFs) and IGF-binding proteins in normal male volunteers.
Glucocorticoids inhibit somatic growth in man and laboratory animals, and have long been regarded as suppressors of both stimulated GH secretion and insulin-like growth factor (IGF) activity. Recent evidence suggests, however, that glucocorticoids can be potent GH secretagogues in their own right with concomitant increases in circulating IGF-I levels. IGFs circulate tightly bound to a group of high-affinity binding proteins (IGFBPs) which modulate their actions. In order to investigate the effects of glucocorticoids on serum levels of IGFs and IGFBPs, normal male volunteers were sampled over 24-h periods before and directly after treatment with dexamethasone (2 mg twice daily) for 96 h. Following dexamethasone administration, all volunteers showed a marked increase in mean +/- S.E.M. IGF-I levels over the 24-h sampling period (292.2 +/- 31.8 before dexamethasone, 425.9 +/- 37 micrograms/l after dexamethasone, P < 0.005); there was no change in mean IGF-II levels. Integrated mean insulin levels were raised by dexamethasone treatment (50 +/- 4.6 before dexamethasone, 117 +/- 13.4 mU/l after dexamethasone, P = 0.002) and IGFBP-1 was significantly suppressed (42.9 +/- 8.2 before dexamethasone, 28.0 +/- 7.9 micrograms/l after dexamethasone, P < 0.001). IGFBP-2 levels were similarly suppressed after dexamethasone (319.5 +/- 24.5 before dexamethasone, 214.8 +/- 8.5 micrograms/l after dexamethasone, P = 0.002), and there was a significant increase in IGFBP-3 levels from 3.24 +/- 0.25 to 3.67 +/- 0.32 mg/l (P = 0.0153). Mean IGF bioactivity over the sampling period after dexamethasone was reduced by approximately 60% (0.93 +/- 0.39 before dexamethasone, 0.39 +/- 0.05 U/ml after dexamethasone, P < 0.0001).(ABSTRACT TRUNCATED AT 250 WORDS)
Miell
J P
JP
Department of Medicine, King's College School of Medicine, London, U.K.
Taylor
A M
AM
Jones
J
J
Holly
J M
JM
Gaillard
R C
RC
Pralong
F P
FP
Ross
R J
RJ
Blum
W F
WF
D000328:Adult; D002352:Carrier Proteins / Q000097:blood*; D003907:Dexamethasone / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000097:blood; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D007335:Insulin-Like Growth Factor II / Q000378:metabolism; D008297:Male; D013002:Somatomedins / Q000378:metabolism*
D002352:Carrier Proteins; D007328:Insulin; D018971:Insulin-Like Growth Factor Binding Protein 2; D018969:Insulin-Like Growth Factor Binding Proteins; D013002:Somatomedins; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II; D003907:Dexamethasone