Posttranslational regulation of TPH1 is responsible for the nightly surge of 5-HT output in the rat pineal gland.

Journal of Pineal Research
Z HuangJimo Borjigin

Abstract

Serotonin (5-hydroxytryptamine, 5-HT), a precursor for melatonin production, is produced abundantly in the pineal gland of all vertebrate animals. The synthesis of 5-HT in the pineal gland is rate limited by tryptophan hydroxylase 1 (TPH1) whose activity displays a twofold increase at night. Earlier studies from our laboratory demonstrate that pineal 5-HT secretion exhibits dynamic circadian rhythms with elevated levels during the early night, and that the increase is controlled by adrenergic signaling at night. In this study, we report that (a) 5-HT total output from the pineal gland and TPH1 protein levels both display diurnal rhythms with a twofold increase at night; (b) stimulation of cAMP signaling elevates 5-HT output in vivo; (c) 5-HT total output and TPH1 protein content in rat pineal gland are both acutely inhibited by light exposure at night. Consistent with these findings, molecular analysis of TPH1 protein revealed that (a) TPH1 is phosphorylated at the serine 58 in vitro and in the night pineal gland; and (b) phosphorylation of TPH1 at this residue is required for cAMP-enhanced TPH1 protein stability. These data support the model that increased nocturnal 5-HT synthesis in the pineal gland is mediated by the phospho...Continue Reading

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Citations

Dec 22, 2009·Reviews in Endocrine & Metabolic Disorders·Asamanja ChattorajJimo Borjigin
Apr 26, 2013·ACS Chemical Neuroscience·Hongyan YangAnne M Andrews
Dec 14, 2011·Journal of Psychopharmacology·Mariana P TorrenteKent E Vrana
Sep 9, 2011·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Anda-Alexandra CalinescuJimo Borjigin
Sep 16, 2014·Chronobiology International·Aneta PiesiewiczPawel M Majewski
Jul 26, 2011·Molecular and Cellular Endocrinology·Jimo BorjiginAnda-Alexandra Calinescu
Mar 26, 2009·Human Mutation·Jeffrey A McKinneyJan Haavik
Mar 10, 2010·Journal of Pineal Research·Zheping HuangJimo Borjigin
May 29, 2016·Developmental and Comparative Immunology·Magdalena MarkowskaKrystyna Skwarło-Sońta
Oct 26, 2016·Journal of Photochemistry and Photobiology. B, Biology·Iwona AdamskaPawel M Majewski
Sep 26, 2013·The American Journal of Gastroenterology·Helmut GrasbergerJuanita L Merchant
Dec 19, 2018·American Journal of Physiology. Endocrinology and Metabolism·Christopher M CarmeanSusumu Seino
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Jul 5, 2019·CNS & Neurological Disorders Drug Targets·Marzieh SeyediNiyaz Mohammadzadeh Honarvar
Oct 28, 2019·General and Comparative Endocrinology·Katarzyna KirszDorota A Zięba

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