{"title":"1α,25(OH)2D3改善小鼠颗粒细胞17β-雌二醇分泌，可能减轻内质网应激。","authors":"Wenjing Lu, Xinjing Shi, Yuning Liu, Haolin Zhang, Zhengrong Yuan, Yingying Han, Qiang Weng","doi":"10.1016/j.bcp.2024.116696","DOIUrl":null,"url":null,"abstract":"<div><div>Vitamin D<sub>3</sub> plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D<sub>3</sub> and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D<sub>3</sub>, 1α,25-dihydroxytamin D<sub>3</sub> [1α,25(OH)<sub>2</sub>D<sub>3</sub>], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)<sub>2</sub>D<sub>3</sub> supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)<sub>2</sub>D<sub>3</sub> stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)<sub>2</sub>D<sub>3</sub> also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10 nM of 1α,25(OH)<sub>2</sub>D<sub>3</sub> activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)<sub>2</sub>D<sub>3</sub>-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.</div></div>","PeriodicalId":8806,"journal":{"name":"Biochemical pharmacology","volume":"232 ","pages":"Article 116696"},"PeriodicalIF":5.3000,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"1α,25(OH)2D3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells\",\"authors\":\"Wenjing Lu, Xinjing Shi, Yuning Liu, Haolin Zhang, Zhengrong Yuan, Yingying Han, Qiang Weng\",\"doi\":\"10.1016/j.bcp.2024.116696\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><div>Vitamin D<sub>3</sub> plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D<sub>3</sub> and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D<sub>3</sub>, 1α,25-dihydroxytamin D<sub>3</sub> [1α,25(OH)<sub>2</sub>D<sub>3</sub>], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)<sub>2</sub>D<sub>3</sub> supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)<sub>2</sub>D<sub>3</sub> stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)<sub>2</sub>D<sub>3</sub> also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10 nM of 1α,25(OH)<sub>2</sub>D<sub>3</sub> activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)<sub>2</sub>D<sub>3</sub>-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.</div></div>\",\"PeriodicalId\":8806,\"journal\":{\"name\":\"Biochemical pharmacology\",\"volume\":\"232 \",\"pages\":\"Article 116696\"},\"PeriodicalIF\":5.3000,\"publicationDate\":\"2025-02-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Biochemical pharmacology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S000629522400697X\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PHARMACOLOGY & PHARMACY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Biochemical pharmacology","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S000629522400697X","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PHARMACOLOGY & PHARMACY","Score":null,"Total":0}
1α,25(OH)2D3 improves 17β-estradiol secretion and potentially alleviates endoplasmic reticulum stress in muskrat granulosa cells
Vitamin D3 plays an essential regulatory role in female reproduction. However, the studies on the correlation between vitamin D3 and muskrat reproduction are limited. This study aims to determine the role of the active form of vitamin D3, 1α,25-dihydroxytamin D3 [1α,25(OH)2D3], on muskrat ovarian granulosa cells (MGCs). The results showed that vitamin D receptor (VDR) was prominently localized in MGCs and 1α,25(OH)2D3 supplementation increased VDR signaling of MGCs. Meanwhile, 10 nM of 1α,25(OH)2D3 stimulated MGCs to secrete 17β-estradiol and enhanced the mRNA expression of steroidogenic enzymes. 1α,25(OH)2D3 also remarkably down-regulated MGCs endoplasmic reticulum stress according to the expression of GRP78, p-PERK, ATF4, and CHOP. In addition, RNA-seq analysis revealed that 10 nM of 1α,25(OH)2D3 activated the PI3K/Akt/mTOR and TNF pathways that contributed to the inhibition of MGCs apoptosis. Taken together, these findings suggest that 1α,25(OH)2D3-induced VDR signaling improves 17β-estradiol secretion and potentially alleviate MGCs endoplasmic reticulum stress through the PERK-ATF4-CHOP pathway.
期刊介绍：
Biochemical Pharmacology publishes original research findings, Commentaries and review articles related to the elucidation of cellular and tissue function(s) at the biochemical and molecular levels, the modification of cellular phenotype(s) by genetic, transcriptional/translational or drug/compound-induced modifications, as well as the pharmacodynamics and pharmacokinetics of xenobiotics and drugs, the latter including both small molecules and biologics.
The journal''s target audience includes scientists engaged in the identification and study of the mechanisms of action of xenobiotics, biologics and drugs and in the drug discovery and development process.
All areas of cellular biology and cellular, tissue/organ and whole animal pharmacology fall within the scope of the journal. Drug classes covered include anti-infectives, anti-inflammatory agents, chemotherapeutics, cardiovascular, endocrinological, immunological, metabolic, neurological and psychiatric drugs, as well as research on drug metabolism and kinetics. While medicinal chemistry is a topic of complimentary interest, manuscripts in this area must contain sufficient biological data to characterize pharmacologically the compounds reported. Submissions describing work focused predominately on chemical synthesis and molecular modeling will not be considered for review.
While particular emphasis is placed on reporting the results of molecular and biochemical studies, research involving the use of tissue and animal models of human pathophysiology and toxicology is of interest to the extent that it helps define drug mechanisms of action, safety and efficacy.
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