SHORT-TERM TASTING IN OBESITY FAILS TO RESTORE THE BLUNTED GH RESPONSIVENESS TO GH-RELEASING HORMONE ALONE OR COMBINED WITH ARGININE

OBJECTIVE Pasting is known to clearly increase both spontaneous and GH RH-stimulated GH secretion in normal subjects and this effect is likel y to be due to hypothalamic mechanism(s). Our aim was to clarify the e ffect of a 3 or 4-day fast, on the GH response to GHRH alone or combin ed with arginine, an amino acid probably acting via inhibition of hypo thalamic somatostatin release. DESIGN Two tests with GHRH (1 mu g/kg i .v.), administered either alone or in combination with arginine (ARG, 0.5g/kg i,v.) were performed, in a randomized order at least 3 days ap art. In obese women the two tests were repeated after a 3 or 4-day fas t. PATIENTS Seven obese women (OB, aged 17-54 years, BMI 42.4 +/- 3.6k g/m(2), waist-hip ratio (WHR) 0.85 +/- 0.01) and ten healthy women, as control subjects (CS, aged 20-44 years, BMI 23.1 +/- 1.1kg/m(2), WHR 0.79 +/- 0.01) were studied. MEASUREMENTS Serum GH and IGF-I levels we re measured by radioimmunoassay. The GH secretory responses were expre ssed either as absolute values (mU/I) or as areas under the curve (AUG , mU/l/h) calculated by trapezoidal integration. IGF-I concentrations were expressed as absolute values (mu g/l) with reference to a pure re combinant IGF-I preparation. Results are expressed as mean +/- SEM, RE SULTS Basal GH and IGF-I levels in OB were lower than in CS (0.8 +/- 0 .2 vs 4.8 +/- 1.0 mU/l, P < 0.0001 and 120.1 +/- 21.4 vs 188.7 +/- 13. 1 mu g/l, P < 0.02, respectively). The GHRH-induced GH rise in OB was lower (P < 0.00001) than in CS (AUG 340.2 +/- 81.0 vs 2125.0 +/- 199.6 mU/l/h). ARG increased the GHRH-induced GH rise in both groups, but i n OB the GH response to ARG +/- GHRH (1458.4 +/- 439.0 mU/l/h, P < 0.0 3 vs GHRH alone) remained lower (P < 0.0001) than in CS (6396.2 +/- 77 2.2 mU/l/h, P < 0.01 vs GHRH alone). In spite of a reduction in body w eight and IGF-I, insulin and glucose levels, in OB fasting failed to m odify both the basal GH levels and the somatotroph responsiveness to G HRH when administered either alone or combined with ARG. An increase i n free fatty acids (PPA) was also found after fasting. CONCLUSIONS The results of this study demonstrate that in obesity the somatotroph hyp oresponsiveness to GHRH, either alone or combined with arginine, is no t improved by short-term fasting, As fasting is considered a CNS media ted stimulus to GH secretion, its ineffectiveness in obesity does not support a hypothalamic pathogenesis and suggests that long standing me tabolic alterations, such as hyperinsulinaemia and/or elevated free fa tty acids, could play a major role in causing GH insufficiency in obes e patients.