E. Ciccarelli et al., HEXARELIN, A SYNTHETIC GROWTH-HORMONE RELEASING PEPTIDE, STIMULATES PROLACTIN SECRETION IN ACROMEGALIC BUT NOT IN HYPERPROLACTINEMIC PATIENTS, Clinical endocrinology, 44(1), 1996, pp. 67-71
OBJECTIVE In man, new synthetic peptides such as hexarelin have been s
hown to have a potent and dose dependent GH releasing activity. Furthe
rmore, a significant PRL releasing activity has also been demonstrated
, but this has been investigated in less detail. We have therefore eva
luated the effect of hexarelin on PRL and GH secretion in patients wit
h active acromegaly or pathological hyperprolactinaemia. DESIGN Hexare
lin (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 admi
nistered in random order on two separate occasions. PATIENTS Eight pat
ients 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 wit
h 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. Basa
l IGF-l was measured in all subjects using an RIA following acid-ethan
ol 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 3
0 (-2566-2040) mU min/l, P < 0.01) and in ACRO (190 (-10-496) vs 6 (-1
00-34) mU/l; 10170 (-5310-51436) vs -82 (-6030-1410) mU min/l, P < 0.0
2), 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 i
ncrease 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). CONCLUSIO
NS Our data show that the PRL releasing effect of hexarelin is preserv
ed in acromegaly but lost in pathological hyperprolactinaemia. In cont
rast with acromegaly, the GH releasing effect of hexarelin is also blu
nted in hyperprolactinaemic patients. These data demonstrate that pati
ents with pathological hyperprolactinaemia are partially refractory to
the activity of hexarelin.