INSULIN-LIKE GROWTH-FACTOR-I AND GROWTH-HORMONE (GH) HAVE DISTINCT AND OVERLAPPING ANABOLIC EFFECTS IN GH-DEFICIENT RATS

The anabolic activity of recombinant human growth hormone (rhGH) and insulin-like growth factor 1 (rhIGF-1) given either alone or together were studied in two models of GH deficiency, hypophysectomized and GH-deficient dwarf rats. A range of rhGH doses (0.08 to 50 mg/kg/day, seven daily sc injections) were given either alone or together with one dose of rhIGF-I (2.4 mg/kg/day, sc infusion). When given alone, or co-administered with rhIGF-1, rhGH produced dose dependent increases in weight gain, bone growth and organ weights. Weight gain in response to rhGH given with rhIGF-1 was comparable to that obtained by a 25-fold higher dose of rhGH given alone. In both animal models absolute weights of the kidneys, liver, spleen and thymus were increased by rhIGF-1 while kidney and liver weight were increased by rhGH. In the hypophysectomized rat, spleen and thymus weights were increased by rhGH but the relative potency of the combination was a 1000-fold that of rhGH alone. The effects of rhIGF-1 and rhGH were additive indicating that the effects of GH or ICF-1 can be greatly increased by their co-administration.