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The serotonin type 3A receptor facilitates luteinizing hormone release and LHβ promoter activity in immortalized pituitary gonadotropes

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Abstract

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-gonadal axis are responsible. To investigate the potential for the 5-HT3AR to modulate gonadotropin release from pituitary gonadotropes, the gonadotrope-derived LβT2 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 LβT2 cells enhanced both basal and GnRH-stimulated LH release and also increased LHβ 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.

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Authors and Affiliations

  1. Medical Sciences Program, Indiana University, Bloomington, IN

    Phillip L. Quirk

  2. Program in Neural Science, Department of Psychology, Indiana University, Cleveland, OH

    Phillip L. Quirk

  3. Department of Pharmacology, Case Western Reserve University, School of Medicine, 10900 Euclid Ave, 44106-4965, Cleveland, OH

    Ruth E. Siegel PhD

Authors
  1. Phillip L. Quirk
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  2. Ruth E. Siegel PhD
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Correspondence to Ruth E. Siegel PhD.

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Quirk, P.L., Siegel, R.E. The serotonin type 3A receptor facilitates luteinizing hormone release and LHβ promoter activity in immortalized pituitary gonadotropes. Endocr 27, 37–43 (2005). https://doi.org/10.1385/ENDO:27:1:037

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  • DOI: https://doi.org/10.1385/ENDO:27:1:037

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