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TAAR1通过鸟氨酸脱羧酶（ODC）在复发性流产中诱导GSK3β磷酸化紊乱。

TAAR1 induces a disturbed GSK3β phosphorylation in recurrent miscarriages through the ODC.

作者信息

Stavrou Stavroula, Gratz Michael, Tremmel Eileen, Kuhn Christina, Hofmann Simone, Heidegger Helene, Peryanova Mina, Hermelink Kerstin, Hutter Stefan, Toth Bettina, Mayr Doris, Mahner Sven, Jeschke Udo, Vattai Aurelia

机构信息

Department of Gynecology and ObstetricsHospital of the LMU, Munich, Germany.

Department of Gynaecological Endocrinology and Reproductive MedicineMedical University Innsbruck, Innsbruck, Austria.

出版信息

Endocr Connect. 2018 Feb;7(2):372-384. doi: 10.1530/EC-17-0272.

DOI:10.1530/EC-17-0272
PMID:29472377
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5825928/
Abstract

OBJECTIVES

Thyroid hormones play an important role in the maintenance of pregnancy. Their derivates, endogenous amines, act via binding to the trace amine-associated receptor (TAAR1). The aim of our study was to analyse the regulation of TAAR1, serine/threonine kinase (pGSK3β) and ornithine decarboxylase (ODC) in placentas of healthy pregnancies, spontaneous (SM) and recurrent miscarriages (RM) and to investigate the influence of thyroid hormone derivates on TAAR1 expression in trophoblast model cells .

METHODS

Patients with SM ( = 15) and RM ( = 15) were compared with patients with healthy pregnancies ( = 15) (pregnancy weeks 7-13 each). Immunohistochemistry was applied to analyse placental TAAR1, pGSK3β and ODC expression. Protein expression of the receptors after stimulation with T, TAM and RO5203548 in BeWo trophoblast model cells was determined via Western blot. Double-immunofluorescence was used to determine placental expression of TAAR1 and ODC.

RESULTS

Levels of TAAR1, pGSK3β and ODC were higher in placentas of RM in comparison to healthy controls. Stimulation of BeWo cells with T, TAM and RO5203548 significantly increased TAAR1 expression. ODC expression in BeWo cells was upregulated through T. Via double-immunofluorescence, TAAR1 and ODC-positive EVT could be detected.

CONCLUSIONS

Upregulation of placental TAAR1 may indicate an increased decarboxylation of thyroid hormones in miscarriages. Patients with RM may have a lack of T through an enhanced transformation of T into TAM induced by the ODC. Future investigations could be carried out to analyse what role a prophylactic T substitution plays for patients.

摘要

目的

甲状腺激素在维持妊娠过程中发挥重要作用。其衍生物内源性胺通过与痕量胺相关受体（TAAR1）结合发挥作用。我们研究的目的是分析健康妊娠、自然流产（SM）和复发性流产（RM）胎盘组织中TAAR1、丝氨酸/苏氨酸激酶（pGSK3β）和鸟氨酸脱羧酶（ODC）的调控情况，并研究甲状腺激素衍生物对滋养层模型细胞中TAAR1表达的影响。

方法

将15例自然流产患者和15例复发性流产患者与15例健康妊娠患者（均处于妊娠7 - 13周）进行比较。采用免疫组织化学方法分析胎盘组织中TAAR1、pGSK3β和ODC的表达。通过蛋白质免疫印迹法测定在BeWo滋养层模型细胞中用甲状腺激素（T）、3,5,3'-三碘甲腺原氨酸（TAM）和RO5203548刺激后受体的蛋白表达情况。采用双重免疫荧光法测定胎盘组织中TAAR1和ODC的表达。

结果

与健康对照组相比，复发性流产胎盘组织中TAAR1、pGSK3β和ODC水平更高。用T、TAM和RO5203548刺激BeWo细胞后，TAAR1表达显著增加。T可上调BeWo细胞中ODC的表达。通过双重免疫荧光法可检测到TAAR1和ODC阳性的绒毛外滋养层细胞（EVT）。

结论

胎盘组织中TAAR1上调可能表明流产时甲状腺激素脱羧作用增强。复发性流产患者可能因ODC诱导T向TAM的转化增强而导致T缺乏。未来可开展研究分析预防性补充T对患者的作用。

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