Mutual priming effects of GHRH and arginine on GH secretion: informative procedure for evaluating GH secretory...

To establish a single and reliable test for evaluating GH secretion, we examined successive GH provocation by two agents with different modes of action: GHRH and arginine (Arg). In 4 normal subjects, a bolus injection of 50 micrograms of GHRH followed by 0.5 g/kg Arg infusion after 90 min evoked two GH peaks and the priming of the GHRH potentiated Arg-induced GH peak by 88% of that by Arg alone. In contrast, Arg pretreatment suppressed the GHRH-induced GH peak to a level of 15%. This inhibitory effect of Arg priming was not recovered by an increase in the GHRH dose (100 micrograms) or by prolongation of the GHRH injection period to 180 min. During Arg infusion, plasma somatostatin (SRIH) was significantly reduced and there was a linear correlation between Arg-induced GH peaks and basal TSH levels. This suggests that GH release by Arg is mediated by suppression of hypothalamic SRIH. One subject showed a blunted GH peak in response to GHRH but a normal peak in response to Arg repeatedly, suggesting an endogenous hypertonicity of SRIH. In 4 other normal subjects, the effect of endogenous GH fluctuation on the GHRH-Arg test was examined in the morning, afternoon and evening. The GH secretory profile was fairly consistent in individuals, but in 2 of them, GH response to GHRH was exaggerated in the evening and Arg-unresponsiveness ensued. This potentiation of GH release appears to be due to an increase in endogenous GHRH secretion or a decrease in SRIH tone. The GHRH-Arg test is therefore able to evaluate GH secretory dynamics through two major mechanisms, GHRH stimulation and SRIH inhibition in a single procedure, reducing the incidence of false negative GH response to Arg.