Acute and short-term effects of growth hormone on insulin-like growth factors and their binding proteins: Serum levels and hepatic messenger ribonucleic acid responses in humans

We investigated the acute (4-5 h) and short-term (5 days) effects of GH tre atment on hepatic messenger RNA (mRNA) levels of the genes for the insulin- like growth factors (IGFs), insulin-like growth factor binding protein-1, - 2, and -3 (IGFBPs), and the acid labile subunit (ALS), as well as serum lev els of these proteins in humans. At the mRNA level, we observed an increase in IGF-1 transcription (+173%) following GH treatment in the acute group, which remained elevated in the short-term treatment group. IGFBP-2 mRNA dec reased after short-term GH treatment, without changes in IGFBP-1 or -3 expr ession. The ALS transcript level increased after 5 days. In serum, we found increased levels of IGF-I and insulin, and decreased levels of IGF-II, in the short-term treatment group. IGFBP-1 decreased in both treatment groups, whereas IGFBP-2 was reduced after 5 days treatment. ALS increased in the s hort-term group. We observed increased IGFBP-3 serum levels after 5 days of GH, treatment, likely due to increased formation of the ternary complex. O ur results show that the metabolic effects by GH on the IGF axis are comple x. In addition to a direct stimulation of IGF-I and ALS expression, GH inhi bits IGFBP-1 serum levels and IGFBP-2 expression in an indirect manner, pos sibly facilitating enhanced IGF bioavailability to target tissues.