title: Serotonin activates cell survival and apoptotic death responses in cultured epithelial thyroid cells.
abstract: Anatomic and physiological interactions between central serotonergic system and thyroid gland are well established. However, the effects of locally available serotonin on the thyroid functions are poorly known. Here, we first demonstrate the expression of serotonin transporter SERT and 5-HT2A receptor subtype in rat thyroid epithelial cell line FRT both at mRNA and protein levels. In order to investigate the molecular mechanisms of serotonin action, FRT cells were exposed to increasing concentrations of the amine. Low concentrations of serotonin (up to 5 μM) enhanced FRT cell growth, and ERK1/2 and SMAD2/3 phosphorylation. Cell exposure to the selective 5-HT2A receptor agonist DOI recapitulated the effects of 5-HT on ERK1/2 phosphorylation. By contrast, administration of M100907, a specific 5-HT2A receptor inhibitor, prevented 5-HT induced ERK1/2 activation. On the other hand, high doses of serotonin (50 μM up to 1 mM) activated a caspase-3 mediated apoptosis of cells. Overall, our findings demonstrate that low levels of serotonin, interacting with 5-HT2A receptor, are able to activate proliferative signals in the thyroid epithelial cells, while high levels of serotonin cause pro-apoptotic responses, thus suggesting an active role of the amine in the thyroid functions and disorders.
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy; Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Giuliana
authors.initials: G
authors.lastname: Cerulo
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Tafuri
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: De Pasquale
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Silviana
authors.initials: S
authors.lastname: Rea
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy.
authors.forename: Simona
authors.initials: S
authors.lastname: Romano
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Costagliola
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Rossella
authors.initials: R
authors.lastname: Della Morte
authors.affiliation: Department of Veterinary Medicine and Animal Productions, University of Naples Federico II, Naples, Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Avallone
authors.affiliation: Department of Molecular Medicine and Medical Biotechnology, University of Naples Federico II, Naples, Italy. Electronic address: luigimichele.pavone@unina.it.
authors.forename: Luigi Michele
authors.initials: LM
authors.lastname: Pavone
mesh_terms: D000818:Animals; D017209:Apoptosis; D002460:Cell Line; D002470:Cell Survival / Q000235:genetics; D004847:Epithelial Cells / Q000378:metabolism; D005464:Fluorobenzenes / Q000008:administration & dosage; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010880:Piperidines / Q000008:administration & dosage; D016601:RNA-Binding Proteins / Q000096:biosynthesis*; D051381:Rats; D044402:Receptor, Serotonin, 5-HT2A / Q000096:biosynthesis*; D012701:Serotonin / Q000008:administration & dosage* / Q000378:metabolism; D013961:Thyroid Gland / Q000378:metabolism*
chemical_list: D005464:Fluorobenzenes; D010880:Piperidines; D016601:RNA-Binding Proteins; D044402:Receptor, Serotonin, 5-HT2A; C482440:Sert1 protein, rat; D012701:Serotonin; C079049:volinanserin
keywords: 5-HT2A receptor; ERK1/2; Rat thyroid epithelial cell line; SERT; Serotonin