Growth hormone response to long-term GH-RH administration in lambs

The pattern of long-term GHRH administration capable of stimulating GH rele ase without depleting pituitary GH content has been investigated using two experimental approaches. In experiment 1, recently weaned male lambs were t reated for 3 weeks as follows: Group A) control; B) subcutaneous (sc) conti nuous infusion of GHRH (1200 mg/day) using a slow release pellet; C) the sa me as B plus 1 daily sc injection of long acting somatostatin (SS) (octreot ide, 20 mg); D) 3 daily sc GHRH (250 mg) injections; E) 2 daily sc injectio ns of GHRH (250 mg) and 2 of natural SS (250 mg). In experiment 2, recently weaned male lambs were continuously GHRH-treated using sc osmotic minipump s (900 mg/day) alone or combined with a daily sc injection of octreotide (2 0 mg) for 4 weeks. Basal plasma GH levels were increased after chronic puls atile GHRH treatment but not after any kind of continuous GHRH administrati on This increment was maintained during the 3 weeks of experimentation and appeared accompanied by a pituitary GH content similar to controls. A marke d GH response to the iv GHRH challenge was observed in controls and in lamb s receiving both types of continuous sc GHRH infusions, whereas pulsatile s c GHRH-treated animals did not respond to the iv GHRH challenge in the firs t and second weeks of the study but did so in the third week of treatment. These data demonstrate that long-term pulsatile GHRH administration is capa ble of stimulating GH release in growing male lambs, without producing pitu itary desensitization.