The effect of recombinant IGF‐I on anterior pituitary function in healthy volunteers

Abstract

Insulin-like growth factor-I is the mediator of many of the actions of GH and is a potent metabolic regulator. Recombinant IGF-I (rhIGF-I) is of potential value in the treatment of syndromes associated with either GH or insulin resistance. This study was designed to assess the effects of subcutaneous (s.c.) rhIGF-I on anterior pituitary function. Double-blind, placebo controlled, randomized cross-over study. The interval between investigations was 2 weeks. Twelve normal volunteers received on one occasion a single s.c. dose of 40 micrograms/kg rhIGF-I and on the other, placebo. Circulating levels were measured, over 24 hours, of GH, LH, FSH, PRL, TSH, cortisol, ACTH, glucose, IGF-I, IGF-II, insulin, C-peptides; IGF binding proteins by Western ligand blotting; total IGF bioactivity using FRTL-5 thyroid cells; and glucose by the glucose oxidase method. Recombinant IGF-I increased AUC for plasma IGF-I, measured by radioimmunoassay (rhIGF-I mean 7065 +/- SEM 33 vs 3895 +/- 204 micrograms/l, P < 0.0001) and IGF bioactivity (22.5 +/- 3.4 vs 14.2 +/- 1.8 U/ml, P < 0.001) but plasma IGF-II fell (9308 +/- 403 vs 11052 +/- 451 micrograms/l, P < 0.0001). There was no biochemical or clinical evidence of hypoglycaemia and no difference in mean glucose levels. No difference existed in AUC for GH, LH, FSH, ACTH and cortisol between rhIGF-I and placebo; additionally, pulse number and amplitude for GH and LH were unaffected. TSH fell following rhIGF-I (33.0 +/- 3.36 vs 42.5 +/- 5.98 mU h/l, P = 0.01). Both mean plasma C-peptide (0.73 +/- 0.06 vs 0.91 +/- 0.05 nmol/l, P = 0.03), and insulin (10.81 +/- 1.02 vs 15.36 +/- 1.18 mU/l, P = 0.03) were lower following rhIGF-I. There was no change in IGFBPs. A single injection of 40 micrograms/kg of subcutaneous rhIGF-I does not cause hypoglycaemia. IGF bioactivity was increased without inhibition of GH secretion. The only change observed in anterior pituitary function was a fall in plasma TSH.