Reduction of the somatotrope responsiveness to GHRH and Hexarelin but not to arginine plus GHRH in hyperprolactinemic patients

Aim of the present study was to verify the maximal secretory capacity of somatotrope cells in patients with pathological hyperprolactinemia (HPRL) comparing it with that in normal age-matched women (NW). To this goal in 12 HPRL normal weight patients (age 28.6±2.6 yr, BMI 23.1 ±1.1 kg/m2) and 8 NW (27.2±0.8 yr, 22.8±0.8 kg/m2) we studied the GH response to GHRH (1µg/kg iv), GHRH plus arginine (ARG, 0.5 g/kg iv), an amino acid probably acting at the hypothalamic level inhibiting somatostatin release, and Hexarelin (HEX, 2 µg/kg iv), a synthetic hexapeptide belonging to GHRP family, which acts concomitantly at the pituitary and the hypothalamic level. IGF-I levels in HPRL were similar to those in NW (179.2±16.5 µg/l and 218.5±30.8 µg/l). In NW the GH response to GHRH (AUC: 1299.5±186.9 µg.90 min/l) was lower (p<0.02) than those to GHRH+ARG (5252.7±846.3 µg.90 min/l) and HEX (3216.6±462.3 µg.90 min/l) which, in turn, were similar. In HPRL the GH response to GHRH (894.7±242.4 µg.90 min/l) was lower (p<0.03) than that to HEX (1586.5±251.3 µg.90 min/l) and both were lower (p<0.03) than that to GHRH+ARG (4468.8±941.7 µg.90 min/l). In HPRL the GH responses to GHRH and HEX were lower than those that in NW (p<0.03) while that to GHRH+ARG was similar in both groups. These results demonstrate that the somatotrope responsiveness to GHRH and HEX is clearly reduced in patients with pathological hyperprolactinemia. On the other hand, in this condition the GH response to GHRH+ARG is normal. As arginine likely acts via inhibition of hypothalamic somatostatin release, these findings show that the maximal secretory capacity of somatotrope cells in hyperprolactinemia is preserved and indicate that partial refractoriness of somatotrope cells to GHRH and HEX could be due to somatostatinergic hyperactivity.