The serotonin type 3A receptor facilitates luteinizing hormone release and LHbeta promoter activity in immortalized pituitary gonadotropes.
The 5-hydroxytryptamine type 3A receptor (5-HT3AR) is a ligand-gated cation channel activated by serotonin. This receptor is expressed throughout the nervous system as well as in the pituitary gland. Although it has been documented that the 5-HT3AR modulates exocytosis in neurons, its role in the pituitary gland has not been determined. Previous research has shown that the 5-HT3AR modulates circulating gonadotropin levels in vivo. It is unclear, however, if its activation in the pituitary gland mediates these effects or if receptors elsewhere in the hypothalamus-pituitary-gondal axis are responsible. To investigate the potential for the 5-HT3AR to modulate gonadotropin release from pituitary gonadotropes, the gonadotrope-derived LbetaT2 cell line was used as a model system and radioimmunoassays were employed to investigate how 5-HT3AR activation influences luteinizing hormone (LH) release. Our studies demonstrate that gonadotropin releasing hormone (GnRH)-stimulated LH release was decreased by the 5-HT3AR-specific antagonist MDL 72222 in a concentration-dependent manner. In addition, it was found that overexpressing the 5-HT3AR in LbetaT2 cells enhanced both basal and GnRH-stimulated LH release and also increased LHbeta gene promoter activity. These results suggest that the 5-HT3AR may participate in the hypothalamus-pituitary-gonadal axis at the level of the pituitary gonadotrope to mediate pituitary hormone release.
Quirk
Phillip L
PL
Medical Sciences Program, Indiana Universtiy, Bloomington, IN, USA.
Siegel
Ruth E
RE
D000818:Animals; D001645:Biguanides / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D008156:Luciferases / Q000096:biosynthesis / Q000235:genetics; D007986:Luteinizing Hormone / Q000235:genetics* / Q000378:metabolism*; D037101:Luteinizing Hormone, beta Subunit / Q000235:genetics*; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011401:Promoter Regions, Genetic / Q000187:drug effects / Q000235:genetics; D011863:Radioimmunoassay; D051381:Rats; D044406:Receptors, Serotonin, 5-HT3 / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012702:Serotonin Antagonists / Q000494:pharmacology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology; D014326:Tropanes / Q000494:pharmacology
D001645:Biguanides; D037101:Luteinizing Hormone, beta Subunit; D044406:Receptors, Serotonin, 5-HT3; D012702:Serotonin Antagonists; D017366:Serotonin Receptor Agonists; D014326:Tropanes; D007986:Luteinizing Hormone; C065734:1-(3-chlorophenyl)biguanide; D008156:Luciferases; C042253:bemesetron