The growth hormone secretagogue hexarelin stimulates the hypothalamo-pituitary-adrenal axis via arginine vasopressin

GH secretagogues (GHSs) act via specific receptors in the hypo-thalamus and the pituitary gland to release GH. GHSs also stimulate the hypothalamo-pit uitary-adrenal (HPA) axis via central mechanisms probably involving CRH or arginine vasopressin (AVP). We studied the effects of hexarelin, CRH, and d esmopressin, an AVP analog, on the stimulation of the HPA axis in 15 health y young male volunteers. Circulating ACTH, cortisol, GH and PRL concentrati ons were measured for 2 h after the injection of hexarelin, CRH, or desmopr essin alone and the combination of hexarelin plus CRH or hexarelin plus des mopressin. Symptoms during the tests were assessed by visual analog scales. Hexarelin significantly increased ACTH and cortisol release (area under th e curve, 3,444 +/- 696 ng/L.125 min and 45,844 +/- 2,925 nmol/L.125 min, re spectively), and this effect was augmented by the addition of CRH in a dose that on its own produces maximal stimulation (6,580 +/- 1,572 ng/mL.125 mi n and 63,170 +/- 2,616 nmol/L.125 min; P = 0.01 and 0.001, respectively), b ut was not influenced by the addition of desmopressin (3,540 +/- 852 ng/mL. 125 min and 35,319 +/- 3,252 nmol/L.125 min; not significant). CRH on its o wn caused similar or slightly higher ACTH and cortisol release than hexarel in alone. Desmopressin given alone elicited a rapid rise in circulating ACT H and cortisol, but its effects were less than those of any other treatment and were not augmented by hexarelin. Hexarelin also caused significant GH and PRL release, but these effects were not influenced by the coadministrat ion of CRH or desmopressin. Visual analog scales showed an acute small incr ement in appetite with hexarelin. Our data suggest that the effect of GHSs on the HPA axis involve at least in part the stimulation of AVP release. In summary, we have shown that in healthy male volunteers, the effect of hexa relin on the HPA axis does not involve CRH, but may occur through the stimu lation of AVP release.