Hexarelin, a synthetic growth hormone releasing peptide, stimulates prolactin secretion in acromegalic but not in hyperprolactinaemic patients

OBJECTIVE In man, new synthetic peptides such as hexarelin have been shown to have a potent and dose dependent GH releasing activity. Furthermore, a significant PRL releasing activity has also been demonstrated, but this has been investigated in less detail. We have therefore evaluated the effect of hexarelin on PRL and GH secretion in patients with active acromegaly or pathological hyperprolactinaemia. DESIGN Hexarelin (2 mu g/kg i.v.), a modified derivative of GHRP-6 of the following structure: His-2-Me-D-Trp-Ala-Trp-D-Phe-Lys-NH2, or placebo, was administered in random order on two separate occasions. PATIENTS Eight patients with active acromegaly (ACRO, 6 F and 2 M, mean age 61.7 years, range 56-73), 6 with macroadenomas and 2 without radiological signs of tumour, and 6 female patients with pathological hyperprolactinaemia (HPRL, mean age 31.2 years, range 18-47) 5 with microadenomas and 1 with empty sella, were studied. Fourteen normal subjects (NS, 8 F and 6 M, 27.1 years, 24-30) were studied as controls. MEASUREMENTS GH and PRL levels were evaluated every 15 minutes for 2 hours after hexarelin or placebo. Both hormones were measured using commercial IRMA kits. Basal IGF-l was measured in all subjects using an RIA following acid-ethanol extraction. RESULTS Hexarelin induced a significant increase in PRL levels in NS (median, range, Delta peak HEX vs placebo: 150 (-14-402) vs 10 (-34-24) mU/I; Delta AUC HEX vs placebo: 7710 (2100-32540) vs 30 (-2566-2040) mU min/l, P < 0.01) and in ACRO (190 (-10-496) vs 6 (-100-34) mU/l; 10170 (-5310-51436) vs -82 (-6030-1410) mU min/l, P < 0.02), but not in HPRL (10 (-180-80) vs 50 (-100-240) mU/l; -600 (-16996-10140) vs -1950 (-8540-14160)mU min/l). Hexarelin also induced lower increase of GH in HPRL (60 (30-82) vs 1.8 (-0.2-2. 2) mU/l; 2853 (1477.6-4372.6 vs 91.6 (-160.6-174) mU min/l, P < 0.05) than in NS (90.8 (50.6-181) vs 0.8 (-1.2-6.8) mU/l; 6642 (2004-13252.6 vs 42 (456-900) mU min/l, P < 0.01) or in ACRO (117.2 (21.2-420.6 vs 3.8 (-2.2-18) mU/l; 6645 (1554-22138.6 vs 334.6 (-324-1065) mU min/l, P < 0.02). CONCLUSIONS Our data show that the PRL releasing effect of hexarelin is preserved in acromegaly but lost in pathological hyperprolactinaemia. In contrast with acromegaly, the GH releasing effect of hexarelin is also blunted in hyperprolactinaemic patients. These data demonstrate that patients with pathological hyperprolactinaemia are partially refractory to the activity of hexarelin.