ESTROGEN REPLACEMENT DOES NOT RESTORE THE REDUCED GH-RELEASING ACTIVITY OF HEXARELIN, A SYNTHETIC HEXAPEPTIDE, IN POSTMENOPAUSAL WOMEN

Hexarelin (HEX), a synthetic hexapeptide, has a strong and reproducibl e GH-releasing activity in man after intravenous, subcutaneous, intran asal and oral administration. Its effect undergoes age-related variati ons, being reduced in elderly subjects. In spite of evidence in animal s showing that the activity of GH-releasing peptides (GHRPs) is positi vely influenced by oestrogens, in young adults no sex-related differen ce has been found in the GH response to HM or to other GHRPs, We aimed to clarify the influence of the menopause and oestrogens on the GH-re leasing activity of HEX. We studied the GH response to the acute admin istration of the maximal effective dose of HEX (2 mu g/kg i.v.) in 24 young women (YW, age: 27.3+/-0.5 years; body mass index (BMI): 20.7+/- 0.3 mu g/m(2)), 14 post-menopausal women (PW age: 52.9+/-1.2 years; BM I: 23.2+/-0.9 kg/m(2)) and 14 aged women (AW, age: 68.9+/-1.5 years: B MI: 21.7+/-0.7 kg/m(2)). In 10 post-menopausal women the GH response t o HEX was also studied after 3 months of transdermal oestradiol treatm ent (delivery 50 mu g/die). Basal oestrogen and GH levels in PW were l ower than those in YW (oestrogen: 4.8+/-3.6 vs 42.0+/-3.4 pg/ml (means +/-S.E.M), P < 0.001; GH: 1.5+/-0.5 vs 2.9+/-0.6 mu g/l, P < 0.02) and similar to those in AW (oestrogen: 1.3+/-0.4 pg/ml; GH: 0.9+/-0.2 mu g/l). IGF-I levels in PW were not different from those in YW (174.4+/- 11.9 vs 195.5+/-14.9 mu g/l) and higher than those in AW (109.8+/-15.8 mu g/l, P < 0.01), The GH response to HEX in PW (areas under the curv e+/-S.E.M.: 453.6+/-56.0 mu g.min/l) was lower (P < 0.002) than that i n YW (1630.4+/-259.7 mu g.min/l) while it did not differ from that in AW (781.8+/-189.3 mu g.min/l). In PW 3-month oestrogen administration increased oestradiol levels (38.3+/-5.9 vs 0.8+/-0.4 pg/ml, P < 0.001) making them similar to those recorded in YW, while it failed to modif y both basal GH and IGF-I levels (GH: 1.8+/-0.6 vs 1.5+/-0.7 mu g/l; I GF-I: 164.6+/-14.3 vs 175.0+/-12.3 mu g/l). Also the GH response to HE X was not modified by oestradiol treatment (518.4+/-125.6 vs 425.4+/-6 9.3 mu g.min/l). In conclusion, present data confirm the strong GH-rel easing effect of Hexarelin in humans and demonstrate that its activity is already reduced in postmenopausal women to an extent overlapping t hat in elderly women, Moreover, oestrogen treatment is not able to res tore it. Thus, the lack of oestrogens does not seem to account for the reduced somatotroph responsiveness to GHRPs in the post-menopausal pe riod.