SEROTONIN DIRECTLY STIMULATES LUTEINIZING-HORMONE-RELEASING HORMONE-RELEASE FROM GT1-1 CELLS VIA 5-HT7 RECEPTORS

Luteinizing hormone-releasing hormone (LHRH release, which serves as t he primary drive to the hypothalamic-pituitary gonadal axis, is contro lled by many neuromediators. Serotonin has been implicated in this reg ulation. However, it is unclear whether the central effect of serotoni n on LHRH secretion is exerted directly on LHRH neurosecretory neurons or indirectly via multisynaptic pathways. The present studies were un dertaken in order to examine whether LHRH secretion from immortalized LHRH cell lines is directly regulated by serotonin and, if so, to iden tify the receptor subtype involved. 8-hydroxy-2-(di-n-propyl-amino)tet ralin (8-OH-DPAT), a 5-HT1A/7 receptor agonist, stimulated LHRH releas e from GT1-1 cells. This effect was blocked by ritanserin, a 5-HT2/7 r eceptor antagonist, but not by SDZ-216-525, a 5-HT1A antagonist. Basal LHRH release was not affected by the 5-HT2 agonist DOI. Reverse trans cription and polymerase chain reaction technique (RT-PCR) was used in order to identify 5-HT1A and 5-HT7 receptor mRNA in immortalized LHRH cell lines. GT1-1 cells express mRNA for the 5-HT7, but not the 5-HT1A receptor subtypes. These results demonstrate a direct stimulatory eff ect of serotonin on LHRH release via 5-HT7 receptor.