ROLE OF THE SEROTONIN RECEPTOR SUBTYPE 5-HT1D ON BASAL AND STIMULATEDGROWTH-HORMONE SECRETION

At present, four main types of serotonin (5-HT) receptors have been id entified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, t he 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist ino)ethyl]-N-methyl-1H-indole-5 -methanesulfonamide succinate, Sumatriptan, to evaluate the role of 5- HT1D receptors on GH secretion. To this end, several tests with or wit hout sumatriptan were undertaken in normal prepubertal children. Furth ermore, we assessed the effect of Sumatriptan on basal GH secretion an d the GH response to GHRH in obese children. In normal children, Sumat riptan administration (3 mg, sc) resulted in an increase in basal GH l evels at 30 min (7.7 +/- 1.5 mu g/L; P < 0.05) and increased GH respon ses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 mu g/L; P < 0.05). The Suma triptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH r esponse to clonidine or pyridostigmine, as assessed by the peak GH res ponse and the area under the curve. In contrast, it increased the GH r esponse to arginine. In the obese subjects, the GH response to GHRH wa s reduced (7.3 +/- 1.0 us. 29.6 +/- 9.7 mu g/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did no t alter the basal GH value (peak GH, 1.7 +/- 0.3 mu g/L at 30 min). Ho wever, Sumatriptan administration clearly increased the effect of GHRH , resulting in a GH peak of 14.6 +/- 3.1 mu g/L at 30 min (P < 0.01). To assess the specificity of Sumatriptan on anterior pituitary hormone secretion, we studied its effect on TSH and PRL responses to TRH as w ell as LH-releasing hormone-induced LH and FSH secretion. Administrati on of Sumatriptan did not alter the response of any of these hormones. Our results indicate that 5-HT1D receptors have a stimulatory effect on GH secretion, possibly by inhibiting hypothalamic somatostatin rele ase.