A further study on the stimulatory effect of peptide histidine methionine on growth hormone secretion in acromegaly: a dose-related study and a comparison with vasoactive intestinal peptide.

We examined whether the GH-releasing effect of peptide histidine methionine (PHM) in acromegaly may be mediated by activation of pituitary receptors for vasoactive intestinal peptide (VIP), which is structurally similar to but more powerful than PHM in stimulating GH secretion in acromegaly. VIP (50 or 100 micrograms) or PHM (50, 100, or 200 micrograms) was given as an i.v. bolus to 11 patients with active acromegaly, and plasma GH levels were measured before and at intervals up to 120 min after the injection. A paradoxical GH response (> 50% and > 6 micrograms/l above the basal) to 50 or 100 micrograms of VIP was observed in 4 (36%) or 5 (45%) patients, respectively. 2 (18%) patients showed paradoxical GH responses to both 50 and 100 micrograms of PHM, and, interestingly, as many as 5 (45%) patients showed positive GH responses to 200 micrograms of PHM. 3 of these 5 responders to 200 micrograms of PHM were also responders to both doses of VIP. To add to, one of the responders to 100 micrograms of VIP did not show a positive GH response to even 200 micrograms of PHM. These results may suggest that in at least some acromegalics the PHM stimulation of GH secretion is mediated by activation of pituitary VIP receptors by PHM and/or by PHM binding to its specific receptors which may have appeared concomitantly with VIP receptors. However, the occasional heterogeneity of the VIP- and PHM-induced GH responses may suggest that on some somatotroph adenomas either VIP or PHM receptors may appear independently.