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 (E2) for expression of the 5-HT4, -5 and -6 receptor (R) (1), 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, by SB-269970, a 5-HTR7/5A antagonist and by SB-224289, a 5-HTR1B antagonist. The GH response was fully blocked by combined administration of SB-206553+SB-269970 and of SB-206553+ketanserin but not by SB-206553+spiperone. Culturing the aggregates without E2 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 DOI, mCpp and -methyl 5-HT, by 5-CT (agonist at 5-HTR1, 5 and 7), by tryptamine (preferential 5-HTR7 agonist), and by the selective 5-HTR1B agonist CP93129 but not by the 5-HTR1A agonists 8-OH-DPAT and the 5-HTR1B/D agonist sumatriptan. The selective 5-HTR2B agonist BW 723C86 stimulated GH release and the selective 5-HTR2B antagonist SB204741 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.