title: Ghrelin enhances the proliferating effect of thyroid stimulating hormone in FRTL-5 thyroid cells.
abstract: Ghrelin regulates cell proliferation through the growth hormone secretagogue receptor (GHS-R). We confirmed the expression of GHS-R in FRTL-5 thyroid cells and investigated the effects of ghrelin in thyrocytes using FRTL-5 cells. Ghrelin increased intracellular calcium levels but not intracellular cyclic AMP levels. Ghrelin activated Erk within 2min, then activated Akt and STAT3. Erk phosphorylation was inhibited by the calcium inhibitor cyclopiazonic acid (CPA). Ghrelin alone did not stimulate FRTL-5 cell proliferation but enhanced the effects of thyroid stimulating hormone (TSH). Pretreatment with TSH potentiates the growth effects of ghrelin in thyroid cells, and p66Shc, a growth factor receptor adaptor protein, might mediate these synergistic effects. Ghrelin phosphorylated TSH-induced p66Shc, which was inhibited by CPA. Ghrelin did not affect the proliferation of ARO cells, which showed no increased expression of p66Shc after TSH treatment. Thus, ghrelin-induced intracellular calcium signaling enhanced the TSH-induced proliferation of thyrocytes, possibly mediated by the p66Shc pathway.
authors.affiliation: Department of Internal Medicine, Seoul National University College of Medicine, 28 Yeongeon-dong, Jongno-gu, Seoul, Republic of Korea.
authors.forename: Young Joo
authors.initials: YJ
authors.lastname: Park
authors.forename: You Jin
authors.initials: YJ
authors.lastname: Lee
authors.forename: Soon Hee
authors.initials: SH
authors.lastname: Kim
authors.forename: Duck Soon
authors.initials: DS
authors.lastname: Joung
authors.forename: Byung Joo
authors.initials: BJ
authors.lastname: Kim
authors.forename: Insuk
authors.initials: I
authors.lastname: So
authors.forename: Do Joon
authors.initials: DJ
authors.lastname: Park
authors.forename: Bo Youn
authors.initials: BY
authors.lastname: Cho
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D049109:Cell Proliferation; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D054439:Ghrelin / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D051381:Rats; D054440:Receptors, Ghrelin / Q000235:genetics / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D015398:Signal Transduction / Q000502:physiology; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013961:Thyroid Gland / Q000166:cytology* / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D054439:Ghrelin; D054440:Receptors, Ghrelin; C528024:SHC1 protein, human; D050796:STAT3 Transcription Factor; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D013972:Thyrotropin; D000242:Cyclic AMP; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D002118:Calcium