INTRAVENOUS ADMINISTRATION OF RECOMBINANT IGF-I LOWERS SERUM GHRH AND TSH

Recombinant IGF-I was administered as an iv bolus of 75 μg/kg to 10 patients with Laron type dwarfism (3 children aged 9, 11 and 12 years and 7 adults aged 30.6 ± 3.5 years) and to 8 healthy subjects (mean age 19.9 ± 12.1 years) and determinations of IGF-I, GHRH, hGH, TSH, and glucose were made before and at 2, 5, 15, 30, 60, 90, and 120 min. The following effects were observed: a. an immediate, marked and sustained drop in blood glucose (p < 0.001), more prolonged in the patients; b. in both groups, a dramatic rise in plasma hGH (p < 0.01) which peaked at 60-90 min; in the patients this occurred after an initial immediate fall in plasma hGH (p < 0.01); c. a progressive decrease of plasma GHRH and TSH (p < 0.05, 0.02) in both patients and healthy controls. An hypothesis is put forward that acute and time-limited release of somatostatin by IGF-I is the main cause of the hormonal changes registered. As the IGF-I bolus also suppressed circulating insulin levels, the hypoglycemia is considered to be a direct effect of IGF-I.