DOES GROWTH HORMONE RELEASING FACTOR DESENSITIZE THE SOMATOTROPH? INTERPRETATION OF RESPONSES OF GROWTH HORMONE DURING AND AFTER 10‐HOUR INFUSION OF GRF 1–29 AMIDE IN MAN

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Abstract
It is unclear whether growth hormone releasing factor (GRF) administration in vivo may desensitize the somatotroph. To investigate this possibility we have examined the effects of 10‐h infusion of the equipotent 1–29 amide analogue of hpGRF on serum GH levels and on the subsequent GH response to a bolus dose of GRF (1–29). Four normal adult males received an intravenous infusion of 1–29 GRF (1 μg/kg/h) from 0800 to 1800 h, with blood samples taken at 10 min intervals. A 100 μg intravenous bolus dose of GRF was given at 1800 h, and sampling continued for a further 90 min. GH levels were near or below the limit of detection (0·5 mU/1) throughout the control 10 h period. During GRF infusion there was increased GH release with pulses of irregular frequency and amplitude (up to 80 mU/1) continuing throughout the entire infusion period. There was no apparent reduction in total GH released towards the latter part of the infusion. On the control day, 100 μg GRF bolus increased mean (± SEM) GH from 0·82 ± 0·21 mU/1 to a peak of 59·0 ± 44·8 mU/1 (P < 0·002). Following 10‐GRF infusion, responses to bolus injection of GRF were reduced, but variable. In two subjects a small rise in GH levels occurred (basal 6·4 and 7·2 rising to peak values of 11·2 and 23·0 mU/1 respectively). In the other two subjects, GH levels fell but in these the GRF bolus had coincided with a GH peak.The loss of GRF responsiveness after GRF infusion may be due to ‘desensitization’. However the response of GH to GRF bolus injection appears to be partly related to the timing of the bolus with the pulses of GH induced by the previous infusion. Caution is needed in the interpretation of acute GRF tests following a period of GRF exposure.