Growth hormone releasing factor infusion does not sustain elevated GH-levels in normal subjects

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Abstract
To evaluate the dynamics of GH-secretion after infusion of growth hormone releasing factor, human pancreatic growth hormone releasing factor (hpGRF1-44) was infused over 2 and 5 h at a dosage of 100 μg hpGRF1-44/h into 11 healthy subjects. The infusion was started and terminated with a 50 μg hpGRF1-44 bolus injection. In 5 subjects 200 μg TRH was given 4 h after starting the infusion. In addition, 4 healthy subjects received 50 μg hpGRF1-44 bolus injection every 2 h. GRF, somatostatin, GH, Prl, and TSH were measured by radioimmunoassay. The initial 50 μg GRF bolus increased GH-levels in all 11 subjects with a maximum at 30 min (24.1 ± 5.1 ng/ml ± se). However, though hpGRF1-44 was continuously infused and GFR-levels remained elevated, GH decreased to a minimum 270 min after start of infusion (2.6 ± 0.6 ng/ml). The GH-response to the second bolus at the end of the infusion was lower compared to the first response (14.6 ± 3.4 ng/ml after 2 h and 7.6 ± 2.5 ng/ml after 5 h). TRH did not lead to a GH-increase during hpGRF1-44 infusion though Prl and TSH rose normally. The intermittent bolus injection of 50 μg hpGRF1-44 led to continuously decreasing GH-responses to the same GRF-dosage (I. bolus: 16.5 ± 1.6 ng/ml; II. bolus: 4.2 ± 0.8 ng/ml; III. bolus: 3.4 ± 0.5 ng/ml). No change in somatostatin levels was observed. These findings show that GRF infusion or bolus injection in short intervals does not sustain elevated GH-levels. Pituitary GH is either not readily available for continuous GRF-stimulation or GH-secretion may be antagonized by increasing portal somatostatin levels which are not reflected in the peripheral circulation.