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Orchestrated feedback regulation between melatonin and sex hormones involving GPER1-PKA-CREB signaling in the placenta.
Shao, Xuan; Yang, Yun; Liu, Yanlei; Wang, Yongqing; Zhao, Yangyu; Yu, Xin; Liu, Juan; Li, Yu-Xia; Wang, Yan-Ling.
Afiliación
  • Shao X; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • Yang Y; University of Chinese Academy of Sciences, Beijing, China.
  • Liu Y; Beijing Institute for Stem Cell and Regenerative Medicine, Beijing, China.
  • Wang Y; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
  • Zhao Y; University of Chinese Academy of Sciences, Beijing, China.
  • Yu X; Center for Reproductive Medicine, School of Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, China.
  • Liu J; Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • Li YX; Department of Obstetrics and Gynecology, Peking University Third Hospital, Beijing, China.
  • Wang YL; State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
J Pineal Res ; 75(4): e12913, 2023 Dec.
Article en En | MEDLINE | ID: mdl-37746893
ABSTRACT
Maintaining placental endocrine homeostasis is crucial for a successful pregnancy. Pre-eclampsia (PE), a gestational complication, is a leading cause of maternal and perinatal morbidity and mortality. Aberrant elevation of testosterone (T0 ) synthesis, reduced estradiol (E2 ), and melatonin productions have been identified in preeclamptic placentas. However, the precise contribution of disrupted homeostasis among these hormones to the occurrence of PE remains unknown. In this study, we established a strong correlation between suppressed melatonin production and decreased E2 as well as elevated T0 synthesis in PE placentas. Administration of the T0 analog testosterone propionate (TP; 2 mg/kg/day) to pregnant mice from E7.5 onwards resulted in PE-like symptoms, along with elevated T0 production and reduced E2 and melatonin production. Notably, supplementation with melatonin (10 mg/kg/day) in TP-treated mice had detrimental effects on fetal and placental development and compromised hormone synthesis. Importantly, E2 , but not T0 , actively enhanced melatonin synthetase AANAT expression and melatonin production in primary human trophoblast (PHT) cells through GPER1-PKA-CREB signaling pathway. On the other hand, melatonin suppressed the level of estrogen synthetase aromatase while promoting the expressions of androgen synthetic enzymes including 17ß-HSD3 and 3ß-HSD1 in PHT cells. These findings reveal an orchestrated feedback mechanism that maintains homeostasis of placental sex hormones and melatonin. It is implied that abnormal elevation of T0 synthesis likely serves as the primary cause of placental endocrine disturbances associated with PE. The suppression of melatonin may represent an adaptive strategy to correct the imbalance in sex hormone levels within preeclamptic placentas. The findings of this study offer novel evidence that identifies potential targets for the development of innovative therapeutic strategies for PE.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Tipo de estudio: Prognostic_studies Idioma: En Revista: J Pineal Res Asunto de la revista: ENDOCRINOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China
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