Stimulation of growth hormone release by 5-hydroxytryptamine (5-HT) in cultured rat anterior pituitary cell aggregates: evidence for mediation by 5-HT2B, 5-HT7, 5-HT1B, and ketanserin-sensitive receptors.
5-Hydroxytryptamine (5-HT) promotes the release of GH by a hypothalamic site of action. The present study explores a putative pituitary action in a perifused rat anterior pituitary aggregate cell culture system. In aggregates cultured with 1 nM estradiol for expression of the 5-HT4, -5, and -6 receptor (R), 5-HT promptly stimulated GH secretion with a dose dependency between 1 and 10 nM. The effect of 5-HT was partially blocked by methiothepin and methysergide; by SB-206553, a 5-HTR2B/C antagonist; SB-269970, a 5-HTR7/5A antagonist; and SB-224289, a 5-HTR1B antagonist. The GH response was fully blocked by combined administration of SB-206553+SB-269970 and SB-206553+ketanserin but not by SB-206553+spiperone. Culturing the aggregates without estradiol diminished the magnitude of the GH response to 5-HT as well as the impact of 5-HTR7/5 blockade on the response. Basal GH release was stimulated by the 5-HTR2 agonists 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane, m-chlorophenyl piperazine, and alpha-methyl 5-HT; 5-carboxytryptamine (agonist at 5-HTR1, -5, and -7); tryptamine (preferential 5-HTR7 agonist); and the selective 5-HTR1B agonist CP93129 but not the 5-HTR1A agonists 7-(dipropylamino)tetralin-1-ol-8-hydroxy-2-(di-n-propylamino)tetralin and the 5-HTR1B/D agonist sumatriptan. The selective 5-HTR2B agonist BW 723C86 stimulated GH release, and the selective 5-HTR2B antagonist SB-204741 attenuated the GH response to 5-HT. The present data suggest that 5-HT may release GH through a pituitary site of action, and that the 5-HTR2B, 5-HTR7 and 5-HTR1B mediate this response, with possibly an inhibitory component of the 5-HTR1D. The relative contribution of these receptors may be modulated by estrogen.
Papageorgiou
A
A
Laboratory of Cell Pharmacology, University of Leuven, Medical School, Campus Gasthuisberg (O and N), B-3000 Leuven, Belgium.
Denef
C
C
D000818:Animals; D002449:Cell Aggregation; D002478:Cells, Cultured; D013006:Growth Hormone / Q000378:metabolism*; D007650:Ketanserin / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D044403:Receptor, Serotonin, 5-HT2B / Q000187:drug effects / Q000502:physiology*; D011985:Receptors, Serotonin / Q000187:drug effects / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology*
D044403:Receptor, Serotonin, 5-HT2B; D011985:Receptors, Serotonin; C104425:serotonin 7 receptor; D012701:Serotonin; D013006:Growth Hormone; D007650:Ketanserin