THE EFFECT OF RECOMBINANT IGF-I ON ANTERIOR-PITUITARY FUNCTION IN HEALTHY-VOLUNTEERS

OBJECTIVE Insulin-like growth factor-l is the mediator of many of the actions of GH and is a potent metabolic regulator. Recombinant IGF-l ( rhlGF-l) is of potential value in the treatment of syndromes associate d with either GH or insulin resistance. This study was designed to ass ess the effects of subcutaneous (s.c.) rhlGF-l on anterior pituitary f unction. DESIGN Double-blind, placebo controlled, randomized cross-ove r study. The interval between investigations was 2 weeks. SUBJECTS Twe lve normal volunteers received on one occasion a single s.c. dose of 4 0 mu g/kg rhlGF-l and on the other, placebo. MEASUREMENTS Circulating levels were measured, over 24 hours, of GH, LH, FSH, PRL, TSH, cortiso l, ACTH, glucose, IGF-l, IGF-ll, insulin, C-peptide; IGF binding prote ins by Western ligand blotting; total IGF bioactivity using FRTL-5 thy roid cells; and glucose by the glucose oxidase method. RESULTS Recombi nant IGF-l increased AUC for plasma IGF-l, measured by radioimmunoassa y (rhlGF-l mean 7065 +/- SEM 33 vs 3895 +/- 204 mu g/l, P < 0.0001) an d IGF bioactivity (22.5 +/- 3.4 vs 14.2 +/- 1.8 U/ml, P < 0.001) but p lasma IGF-ll fell (9308 +/- 403 vs 11052 +/- 451 mu g/l, P < 0.001). T here was no biochemical or clinical evidence of hypoglycaemia and no d ifference in mean glucose levels. No difference existed in AUC for GH, LH, FSH, ACTH and cortisol between rhlGF-l and placebo; additionally, pulse number and amplitude for GH and LH were unaffected. TSH fell fo llowing rhlGF-l (33.0 +/- 3.36 vs 42.5 +/- 5.98 mU h/l, P = 0.01). Bot h 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/I, P = 0.03) wer e lower following rhlGF-l. There was no change in IGFBPs. CONCLUSION A single injection of 40 mu/kg of subcutaneous rhlGF-l does not cause h ypoglycaemia. IGF bioactivity was increased without inhibition of GH s ecretion. The only change observed in anterior pituitary function was a fall in plasma TSH.