title: Role of the serotonin receptor subtype 5-HT1D on basal and stimulated growth hormone secretion.
abstract: At present, four main types of serotonin (5-HT) receptors have been identified in the brain (5-HT1, 5-HT2, 5-HT3, and 5-HT4). In addition, the 5-HT1 have been further subclassified. We have taken advantage of a new selective 5-HT1D receptor agonist 3-[2-(dimethylamino)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 without sumatriptan were undertaken in normal prepubertal children. Furthermore, we assessed the effect of Sumatriptan on basal GH secretion and the GH response to GHRH in obese children. In normal children, Sumatriptan administration (3 mg, sc) resulted in an increase in basal GH levels at 30 min (7.7 +/- 1.5 micrograms/L; P < 0.05) and increased GH responses to GHRH (47.3 +/- 6.4 vs. 29.6 +/- 9.7 micrograms/L; P < 0.05). The Sumatriptan-induced increase in GH responses to GHRH was dependent on the stimulus tested. Pretreatment with Sumatriptan did not modify the GH response to clonidine or pyridostigmine, as assessed by the peak GH response and the area under the curve. In contrast, it increased the GH response to arginine. In the obese subjects, the GH response to GHRH was reduced (7.3 +/- 1.0 vs. 29.6 +/- 9.7 micrograms/L at 30 min) compared to that in control children (P < 0.05). Sumatriptan administration did not alter the basal GH value (peak GH, 1.7 +/- 0.3 micrograms/L at 30 min). However, Sumatriptan administration clearly increased the effect of GHRH, resulting in a GH peak of 14.6 +/- 3.1 micrograms/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 well as LH-releasing hormone-induced LH and FSH secretion. Administration 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 release.
authors.affiliation: Department of Pediatric, Hospital de D. Estefania, Lisbon, Portugal.
authors.forename: A
authors.initials: A
authors.lastname: Mota
authors.forename: A
authors.initials: A
authors.lastname: Bento
authors.forename: A
authors.initials: A
authors.lastname: Peñalva
authors.forename: M
authors.initials: M
authors.lastname: Pombo
authors.forename: C
authors.initials: C
authors.lastname: Dieguez
mesh_terms: D001120:Arginine / Q000494:pharmacology; D002648:Child; D003000:Clonidine / Q000494:pharmacology; D005260:Female; D005640:Follicle Stimulating Hormone / Q000378:metabolism; D007987:Gonadotropin-Releasing Hormone; D013006:Growth Hormone / Q000378:metabolism*; D013007:Growth Hormone-Releasing Hormone / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D007986:Luteinizing Hormone / Q000378:metabolism; D008297:Male; D009765:Obesity / Q000503:physiopathology; D010903:Pituitary Gland, Anterior / Q000187:drug effects / Q000378:metabolism; D011388:Prolactin / Q000378:metabolism; D011729:Pyridostigmine Bromide / Q000494:pharmacology; D011985:Receptors, Serotonin / Q000502:physiology*; D018170:Sumatriptan / Q000008:administration & dosage / Q000494:pharmacology*; D013972:Thyrotropin / Q000378:metabolism; D013973:Thyrotropin-Releasing Hormone
chemical_list: D011985:Receptors, Serotonin; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D018170:Sumatriptan; D011388:Prolactin; D007986:Luteinizing Hormone; D005640:Follicle Stimulating Hormone; D013972:Thyrotropin; D013006:Growth Hormone; D013007:Growth Hormone-Releasing Hormone; D001120:Arginine; D011729:Pyridostigmine Bromide; D003000:Clonidine