Study summary · research use only
The growth hormone secretagogue hexarelin stimulates the hypothalamo-pituitary-adrenal axis via arginine vasopressin
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This human study examined the GH secretagogue hexarelin and its effect on the hypothalamo-pituitary-adrenal axis in 15 healthy young male volunteers, comparing hexarelin, CRH, and the vasopressin analog desmopressin, given alone and in combinations. Circulating ACTH, cortisol, GH and prolactin were measured for 2 hours after injection. The authors report hexarelin significantly increased ACTH and cortisol release, an effect augmented by adding CRH but not by adding desmopressin. CRH alone produced similar or slightly higher ACTH and cortisol release than hexarelin alone, while desmopressin alone caused a rapid but smaller rise not augmented by hexarelin. Hexarelin also increased GH and prolactin release and was associated with a small increase in appetite. The authors suggest the effect on the HPA axis may involve vasopressin release.
Abstract
GH secretagogues (GHSs) act via specific receptors in the hypothalamus and the pituitary gland to release GH. GHSs also stimulate the hypothalamo-pituitary-adrenal (HPA) axis via central mechanisms probably involving CRH or arginine vasopressin (AVP). We studied the effects of hexarelin, CRH, and desmopressin, an AVP analog, on the stimulation of the HPA axis in 15 healthy young male volunteers. Circulating ACTH, cortisol, GH and PRL concentrations were measured for 2 h after the injection of hexarelin, CRH, or desmopressin alone and the combination of hexarelin plus CRH or hexarelin plus desmopressin. Symptoms during the tests were assessed by visual analog scales. Hexarelin significantly increased ACTH and cortisol release (area under the curve, 3,444+/-696 ng/L x 125 min and 45,844+/-2,925 nmol/L x 125 min, respectively), 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 x 125 min and 63,170+/-2,616 nmol/L x 125 min; P = 0.01 and 0.001, respectively), but was not influenced by the addition of desmopressin (3,540+/-852 ng/mL x 125 min and 35,319+/-3,252 nmol/L x 125 min; not significant). CRH on its own caused similar or slightly higher ACTH and cortisol release than hexarelin alone. Desmopressin given alone elicited a rapid rise in circulating ACTH 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 coadministration of CRH or desmopressin. Visual analog scales showed an acute small increment 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 hexarelin on the HPA axis does not involve CRH, but may occur through the stimulation of AVP release.
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