Influence of different serotonin receptor subtypes on growth hormone secretion

The role of serotonin (5-HT) in the regulation of growth hormone (GH) secre tion remains unclear due to the existence of many different receptors that mediate the 5-HT actions, and the lack of suitable specific agonist and ant agonist drugs. In the present work we have taken advantage of the recent de velopment of new selective 5-HT drugs in order to clarify the role played b y different 5-HT receptor types and subtypes on GH secretion. The experimen ts were carried out on beagle dogs. GH-releasing hormone (GHRH) increased b asal canine GH (cGH) levels from 0.8 +/- 0.2 to 8.8 +/- 1.7 mu g/l at 15 mi n. Administration of 5-HT1D receptor agonist sumatriptan (SUM) induced a cG H peak at 30 min of 12.9 +/- 2.7 mu g/l. The combined administration of GHR H plus SUM strikingly potentiated cGH release with a peak of 36.9 +/- 6 mu g/l at 30 min (p < 0.05). Pretreatment with the muscarinic receptor antagon ist atropine completely abolished the cGH response to SUM, while the cholin ergic agonist pyridostigmine (PYR) did not modify this response (15.3 +/- 5 mu g/l PYR plus SUM vs. SUM alone 12.9 +/- 2.7 mu g/l). On the other hand, administration of drugs with activityDat 5-HT2A/C receptors showed a stimu latory role for the 5-HT2C receptor subtype, since LY-53857 (antagonist 5-H T2A/C) and DOI agonist (5-HT2A/C) both modified the GH response stimulated by GHRH (AUC 88.5 +/- 30.4 and 400 +/- 64.6 vs. 267.3 +/- 52.6 respectively ), while ketanserin (antagonist 5-HT2A) did not modify this response. The 5 -HT3 antagonist ICS-205-930 failed to modify either basal or GHRH induced G H responses. In conclusion, our data show that 5-HT1D receptors play a stim ulatory role on GH secretion in the dog, possibly by acting th rough a decr ease in hypothalamic somatostatin release. Similarly, the 5-HT2C receptor s ubtypes also appear to play a stimulatory role. However, 5-HT2A and 5-HT3 r eceptors do not appear to be involved in the control of basal and GHRH-indu ced GH secretion. Copyright (C) 2000 S. Karger AG, Basel.