Influence of Different Serotonin Receptor Subtypes On Growth Hormone Secretion

The role of serotonin (5-HT) in the regulation of growth hormone (GH) secretion remains unclear due to the existence of many different receptors that mediate the 5-HT actions, and the lack of suitable specific agonist and antagonist drugs. In the present work we have taken advantage of the recent development of new selective 5-HT drugs in order to clarify the role played by different 5-HT receptor types and subtypes on GH secretion. The experiments were carried out on beagle dogs. GH-releasing hormone (GHRH) increased basal canine GH (cGH) levels from 0.8 ± 0.2 to 8.8 ± 1.7 µg/l at 15 min. Administration of 5-HT1D receptor agonist sumatriptan (SUM) induced a cGH peak at 30 min of 12.9 ± 2.7 µg/l. The combined administration of GHRH plus SUM strikingly potentiated cGH release with a peak of 36.9 ± 6 µg/l at 30 min (p < 0.05). Pretreatment with the muscarinic receptor antagonist atropine completely abolished the cGH response to SUM, while the cholinergic agonist pyridostigmine (PYR) did not modify this response (15.3 ± 5 µg/l PYR plus SUM vs. SUM alone 12.9 ± 2.7 µg/l). On the other hand, administration of drugs with activity at 5-HT2A/C receptors showed a stimulatory role for the 5-HT2C receptor subtype, since LY-53857 (antagonist 5-HT2A/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 GH responses. In conclusion, our data show that 5-HT1D receptors play a stimulatory role on GH secretion in the dog, possibly by acting through a decrease in hypothalamic somatostatin release. Similarly, the 5-HT2C receptor subtypes also appear to play a stimulatory role. However, 5-HT2A and 5-HT3 receptors do not appear to be involved in the control of basal and GHRH-induced GH secretion.

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