Journal of molecular endocrinology最新文献_第5页

Conserved and divergent features of trophoblast stem cells. 滋养层干细胞的保守和分化特征

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-02-19 Print Date: 2024-05-01 DOI: 10.1530/JME-23-0131

Nirvay Sah, Francesca Soncin

{"title":"Conserved and divergent features of trophoblast stem cells.","authors":"Nirvay Sah, Francesca Soncin","doi":"10.1530/JME-23-0131","DOIUrl":"10.1530/JME-23-0131","url":null,"abstract":"Trophoblast stem cells (TSCs) are a proliferative multipotent population derived from the trophectoderm of the blastocyst, which will give rise to all the functional cell types of the trophoblast compartment of the placenta. The isolation and culture of TSCs in vitro represent a robust model to study mechanisms of trophoblast differentiation into mature cells both in successful and diseased pregnancy. Despite the highly conserved functions of the placenta, there is extreme variability in placental morphology, fetal-maternal interface, and development among eutherian mammals. This review aims to summarize the establishment and maintenance of TSCs in mammals such as primates, including human, rodents, and nontraditional animal models with a primary emphasis on epigenetic regulation of their origin while defining gaps in the current literature and areas of further development. FGF signaling is critical for mouse TSCs but dispensable for derivation of TSCs in other species. Human, simian, and bovine TSCs have much more complicated requirements of signaling pathways including activation of WNT and inhibition of TGFβ cascades. Epigenetic features such as DNA and histone methylation as well as histone acetylation are dynamic during development and are expressed in cell- and gestational age-specific pattern in placental trophoblasts. While TSCs from different species seem to recapitulate some select epigenomic features, there is a limitation in the comprehensive understanding of TSCs and how well TSCs retain placental epigenetic marks. Therefore, future studies should be directed at investigating epigenomic features of global and placental-specific gene expression in primary trophoblasts and TSCs.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11008758/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139564368","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K. 卵泡刺激素通过增强甲基转移酶样 3 介导的 cathepsin K m6A 甲基化加速破骨细胞迁移。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-02-14 Print Date: 2024-04-01 DOI: 10.1530/JME-23-0130

Xiaosa Li, Chao Fan, Jiale Wang, Ping Li, Xingyan Xu, Ruixin Guo, Jinzhi Wei, Yang Cheng, Huiping Lin, Xiaodong Fu

{"title":"Follicle-stimulating hormone accelerates osteoclast migration by enhancing methyltransferase-like 3-mediated m6A methylation of cathepsin K.","authors":"Xiaosa Li, Chao Fan, Jiale Wang, Ping Li, Xingyan Xu, Ruixin Guo, Jinzhi Wei, Yang Cheng, Huiping Lin, Xiaodong Fu","doi":"10.1530/JME-23-0130","DOIUrl":"10.1530/JME-23-0130","url":null,"abstract":"Follicle-stimulating hormone (FSH) accelerates osteoporosis in postmenopausal women, while the underlying mechanism remains uncharacterized. N6-methyladenosine (m6A) is one of the most important regulations in the development of osteoporosis. In this study, we aimed to investigate the role of FSH in m6A modification and osteoclast function. Here, we showed that FSH upregulated m6A levels in osteoclasts via stimulating methyltransferase-like 3 (METTL3) protein expression. FSH enhanced osteoclast migration, while the knockdown of METTL3 eliminated this enhancement. Both MeRIP-seq and RNA sequencing identified that cathepsin K (CTSK) is the potential downstream target of METTL3. Knockdown of CTSK reduced FSH-upregulated osteoclast migration. Furthermore, silencing METTL3 decreased CTSK mRNA stability. Finally, FSH induced phosphorylation of cyclic-AMP response element-binding protein (CREB), while silencing of CREB attenuated the effects of FSH on the promoter transcriptional activity of Mettl3 and CTSK/METTL3 protein. Taken together, these findings indicate that FSH promotes osteoclast migration via the CREB/METTL3/CTSK signaling pathway, which may provide a potential target for suppressing osteoclast mobility and postmenopausal osteoporosis therapy.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139521110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

No extra-adrenal aldosterone production in various human cell lines. 在各种人类细胞系中均未产生肾上腺外醛固酮。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-02-01 Print Date: 2024-04-01 DOI: 10.1530/JME-23-0100

Isabelle Durrer, Daniel Ackermann, Rahel Klossner, Michael Grössl, Clarissa Vögel, Therina Du Toit, Bruno Vogt, Heidi Jamin, Markus G Mohaupt, Carine Gennari-Moser

{"title":"No extra-adrenal aldosterone production in various human cell lines.","authors":"Isabelle Durrer, Daniel Ackermann, Rahel Klossner, Michael Grössl, Clarissa Vögel, Therina Du Toit, Bruno Vogt, Heidi Jamin, Markus G Mohaupt, Carine Gennari-Moser","doi":"10.1530/JME-23-0100","DOIUrl":"10.1530/JME-23-0100","url":null,"abstract":"Extra-adrenal de novo aldosterone (Aldo) production has been described inconsistently. Systematic data based upon state-of-the-art technology including validated controls are sparse. We hypothesized that aldosterone synthase (CYP11B2) expression and de novo Aldo production are absent in nonadrenal human cell lines, either immortalized cell lines or commercially available primary cell lines, including peripheral blood mononuclear cells (PBMCs) of individuals without and with primary hyperaldosteronism (PA). CYP11B2-transfected COS-7 and endogenous CYP11B2 expressing adrenal H295R cells served as positive controls. Various well-characterized, purchased, immortalized (BeWo, HEK293, HTR-8/SVneo, JEG-3) and primary (HAEC, HLEC, HRGEC, HRMC, HUAEC, HUVEC, PBMC) cell lines as well as self-isolated PBMCs from PA patients (n = 5) were incubated with the steroid hormone substrates progesterone, deoxycorticosterone, corticosterone or 18-OH-corticosterone with and without Ang II for 24 h to assess CYP11B2 enzymatic activity. CYP11B2 expression was analyzed by real-time PCR and liquid chromatography-mass spectrometry was used to quantify Aldo production. Pronounced CYP11B2 mRNA expression and Aldo production were observed in both positive controls, which followed an incremental time course. Neither substrates alone nor coincubation with Ang II significantly stimulated CYP11B2 expression or Aldo production in various immortalized and primary cell lines and PBMCs of PA patients. These results strongly support the absence of relevant de novo extra-adrenal Aldo production in nonadrenal cells, including blood mononuclear cells, irrespective of the absence or presence of autonomous adrenal Aldo production.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10895282/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139098049","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

AMPK-mTORC1 pathway mediates hepatic IGFBP-1 phosphorylation in glucose deprivation: a potential molecular mechanism of hypoglycemia-induced impaired fetal growth. AMPK-mTORC1通路在葡萄糖剥夺过程中介导肝脏IGFBP-1磷酸化。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-01-31 Print Date: 2024-04-01 DOI: 10.1530/JME-23-0137

Jenica H Kakadia, Muhammad U Khalid, Ilka U Heinemann, Victor K Han

{"title":"AMPK-mTORC1 pathway mediates hepatic IGFBP-1 phosphorylation in glucose deprivation: a potential molecular mechanism of hypoglycemia-induced impaired fetal growth.","authors":"Jenica H Kakadia, Muhammad U Khalid, Ilka U Heinemann, Victor K Han","doi":"10.1530/JME-23-0137","DOIUrl":"10.1530/JME-23-0137","url":null,"abstract":"Mechanisms underlying limitations in glucose supply that restrict fetal growth are not well established. IGF-1 is an important regulator of fetal growth and IGF-1 bioavailability is markedly inhibited by IGFBP-1 especially when the binding protein is hyperphosphorylated. We hypothesized that the AMPK-mTORC1 pathway increases IGFBP-1 phosphorylation in response to glucose deprivation. Glucose deprivation in HepG2 cells activated AMPK and TSC2, inhibited mTORC1 and increased IGFBP-1 secretion and site-specific phosphorylation. Glucose deprivation also decreased IGF-1 bioavailability and IGF-dependent activation of IGF-1R. AICAR (an AMPK activator) activated TSC2, inhibited mTORC1, and increased IGFBP-1 secretion/phosphorylation. Further, siRNA silencing of either AMPK or TSC2 prevented mTORC1 inhibition and IGFBP-1 secretion and phosphorylation in glucose deprivation. Our data suggest that the increase in IGFBP-1 phosphorylation in response to glucose deprivation is mediated by the activation of AMPK/TSC2 and inhibition of mTORC1, providing a possible mechanistic link between glucose deprivation and restricted fetal growth.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10895286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139403321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Oxidative and ER stress by elevated insulin biosynthesis and palmitic acid in insulin-producing cells. 胰岛素分泌细胞中胰岛素生物合成和棕榈酸升高导致的氧化和ER压力。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-01-11 Print Date: 2024-02-01 DOI: 10.1530/JME-23-0087

Brenda Vidrio-Huerta, Thomas Plötz, Stephan Lortz

{"title":"Oxidative and ER stress by elevated insulin biosynthesis and palmitic acid in insulin-producing cells.","authors":"Brenda Vidrio-Huerta, Thomas Plötz, Stephan Lortz","doi":"10.1530/JME-23-0087","DOIUrl":"10.1530/JME-23-0087","url":null,"abstract":"The early phase of type 2 diabetes mellitus (T2DM) is characterised by insulin resistance, which can initially be compensated by elevated insulin secretion. However, as postulated by the workload hypothesis, over time harming insulin requirements contribute to β-cell dysfunction and death. The mechanisms behind this transition are complex and not fully understood but involve factors such as endoplasmic reticulum (ER) stress raised by gluco/lipotoxicity. To investigate the effect of excessive insulin folding on ER luminal H2O2 generation, ER stress and viability, insulin was expressed glucose-independently by a doxycycline-regulated Tet-On system in insulin-producing RINm5F cells. Additionally, the effect of palmitic acid (PA) as a subsidiary T2DM-associated factor was examined in this model system. Elevated insulin expression increased ER luminal H2O2 concentration quantified by the fluorescent sensor protein TriPer and reduced viability, but did not activate apoptosis. However, when combined with PA, insulin expression resulted in a significant increase in ER stress and apoptosis. Expression of ER-localised catalase verified the specificity of the applied H2O2 detection method without attenuating ER stress, caspase activation or viability loss. These findings suggest that hyperinsulinism alone can cause increased ER luminal H2O2 generation, mild ER stress and reduced viability, while hyperinsulinism in combination with PA accelerates these processes and triggers apoptosis. The inability of ER catalase to counteract these effects suggests that further damaging factors besides H2O2 are involved in cell dysfunction. Finally, reducing the high insulin demand in the initial phase of T2DM may be crucial in preventing further β-cell damage caused by gluco/lipotoxicity.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138487817","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

N1-methylnicotinamide impairs gestational glucose tolerance in mice. n1 -甲基烟酰胺损害小鼠妊娠期葡萄糖耐量。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2024-01-08 Print Date: 2024-02-01 DOI: 10.1530/JME-23-0126

Xiaojing Wei, Yutian Tan, Jiaqi Huang, Ximing Dong, Weijie Feng, Tanglin Liu, Zhao Yang, Guiying Yang, Xiao Luo

{"title":"N1-methylnicotinamide impairs gestational glucose tolerance in mice.","authors":"Xiaojing Wei, Yutian Tan, Jiaqi Huang, Ximing Dong, Weijie Feng, Tanglin Liu, Zhao Yang, Guiying Yang, Xiao Luo","doi":"10.1530/JME-23-0126","DOIUrl":"10.1530/JME-23-0126","url":null,"abstract":"N1-methylnicotinamide (MNAM), a product of methylation of nicotinamide through nicotinamide N-methyltransferase, displays antidiabetic effects in male rodents. This study aimed to evaluate the ameliorative potential of MNAM on glucose metabolism in a gestational diabetes mellitus (GDM) model. C57BL/6N mice were fed with a high-fat diet (HFD) for 6 weeks before pregnancy and throughout gestation to establish the GDM model. Pregnant mice were treated with 0.3% or 1% MNAM during gestation. MNAM supplementation in CHOW diet and HFD both impaired glucose tolerance at gestational day 14.5 without changes in insulin tolerance. However, MNAM supplementation reduced hepatic lipid accumulation as well as mass and inflammation in visceral adipose tissue. MNAM treatment decreased GLUT4 mRNA and protein expression in skeletal muscle, where NAD+ salvage synthesis and antioxidant defenses were dampened. The NAD+/sirtuin system was enhanced in liver, which subsequently boosted hepatic gluconeogenesis. GLUT1 protein was diminished in placenta by MNAM. In addition, weight of placenta, fetus weight, and litter size were not affected by MNAM treatment. The decreased GLUT4 in skeletal muscle, boosted hepatic gluconeogenesis and dampened GLUT1 in placenta jointly contribute to the impairment of glucose tolerance tests by MNAM. Our data provide evidence for the careful usage of MNAM in treatment of GDM.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-01-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10831565/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138460427","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Development and characterisation of a novel inhibitory anti-GH monoclonal antibody. 一种新型抑制性抗生长激素单克隆抗体的研制和表征。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2023-12-13 Print Date: 2024-01-01 DOI: 10.1530/JME-23-0071

Man Lu, Chantal Buckley, Yue Wang, Ries J Langley, Jo K Perry

{"title":"Development and characterisation of a novel inhibitory anti-GH monoclonal antibody.","authors":"Man Lu, Chantal Buckley, Yue Wang, Ries J Langley, Jo K Perry","doi":"10.1530/JME-23-0071","DOIUrl":"10.1530/JME-23-0071","url":null,"abstract":"Excess growth hormone (GH) has been implicated in multiple cancer types and there is increasing interest in the development of therapeutic inhibitors targeting GH-GH receptor (GHR) signalling. Here we describe a panel of anti-GH monoclonal antibodies (mAbs) generated using a hybridoma approach and identify two novel inhibitory mAbs (1-8-2 and 1-46-3) that neutralised GH signalling. mAbs 1-8-2 and 1-46-3 exhibited strong inhibitory activity against GH-dependent cell growth in a Ba/F3-GHR cell viability assay, with EC50 values of 1.00 ± 0.27 and 0.5 ± 0.1 µg/mL, respectively. Cross-reactivity with the human placental hormones, placental lactogen (PL) and placental GH, was observed by ELISA, but neither antibody cross-reacted with mouse GH or human prolactin (PRL). mAb 1-8-2 had a binding affinity for GH of KD 0.62 ± 0.5 nM, while mAb 1-46-3 had a KD of 2.68 ± 0.53 nM, as determined by bio-layer interferometry. mAb 1-46-3 inhibited GH-dependent signal transduction in T-47D and LNCaP cancer cell lines and reduced GH-dependent cell growth and migration in the breast cancer cell line T-47D. mAb 1-46-3 inhibited T-47D cell viability more effectively than the GHR antagonist B2036. In conclusion, we describe two novel inhibitory anti-GH mAbs and provide in vitro evidence supporting development of these entities as anti-cancer therapeutics.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"49678603","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Pseudohypoparathyroidism: complex disease variants with unfortunate names. 假性甲状旁腺功能减退症:复杂的疾病变体与不幸的名称。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2023-12-12 Print Date: 2024-01-01 DOI: 10.1530/JME-23-0104

Harald Jüppner

{"title":"Pseudohypoparathyroidism: complex disease variants with unfortunate names.","authors":"Harald Jüppner","doi":"10.1530/JME-23-0104","DOIUrl":"10.1530/JME-23-0104","url":null,"abstract":"Several human disorders are caused by genetic or epigenetic changes involving the GNAS locus on chromosome 20q13.3 that encodes the alpha-subunit of the stimulatory G protein (Gsα) and several splice variants thereof. Thus, pseudohypoparathyroidism type Ia (PHP1A) is caused by heterozygous inactivating mutations involving the maternal GNAS exons 1-13 resulting in characteristic abnormalities referred to as Albright's hereditary osteodystrophy (AHO) that are associated with resistance to several agonist ligands, particularly to parathyroid hormone (PTH), thereby leading to hypocalcemia and hyperphosphatemia. GNAS mutations involving the paternal Gsα exons also cause most of these AHO features, but without evidence for hormonal resistance, hence the term pseudopseudohypoparathyroidism (PPHP). Autosomal dominant pseudohypoparathyroidism type Ib (PHP1B) due to maternal GNAS or STX16 mutations (deletions, duplications, insertions, and inversions) is associated with epigenetic changes at one or several differentially methylated regions (DMRs) within GNAS. Unlike the inactivating Gsα mutations that cause PHP1A and PPHP, hormonal resistance is caused in all PHP1B variants by impaired Gsα expression due to loss of methylation at GNAS exon A/B, which can be associated in some familial cases with epigenetic changes at the other maternal GNAS DMRs. The genetic defect(s) responsible for sporadic PHP1B, the most frequent variant of this disorder, remain(s) unknown for the majority of patients. However, characteristic epigenetic GNAS changes can be readily detected that include a gain of methylation at the neuroendocrine secretory protein (NESP) DMR. Multiple genetic or epigenetic GNAS abnormalities can thus impair Gsα function or expression, consequently leading to inadequate cAMP-dependent signaling events downstream of various Gsα-coupled receptors.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10843601/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"107591503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Retinoic acid regulation of homoeostatic synaptic plasticity and its relationship to cognitive disorders. 维甲酸对稳态突触可塑性的调节及其与认知障碍的关系。

IF 3.8 4区医学

Journal of molecular endocrinology Pub Date : 2023-12-06 Print Date: 2024-01-01 DOI: 10.1530/JME-22-0177

Francesca Moramarco, Peter McCaffery

{"title":"Retinoic acid regulation of homoeostatic synaptic plasticity and its relationship to cognitive disorders.","authors":"Francesca Moramarco, Peter McCaffery","doi":"10.1530/JME-22-0177","DOIUrl":"10.1530/JME-22-0177","url":null,"abstract":"There is increasing interest in retinoic acid (RA) as a regulator of the complex biological processes underlying the cognitive functions performed by the brain. The importance of RA in brain function is underlined by the brain's high efficiency in converting vitamin A into RA. One crucial action of RA in the brain is dependent on RA receptor α (RARα) transport out of the nucleus, where it no longer regulates transcription but carries out non-genomic functions. RARα, when localised in the cytoplasm, particularly in neuronal dendrites, acts as a translational suppressor. It regulates protein translation as a crucial part of the mechanism maintaining homoeostatic synaptic plasticity, which is characterised by neuronal changes necessary to restore and balance the excitability of neuronal networks after perturbation events. Under normal conditions of neurotransmission, RARα without ligand suppresses the translation of proteins. When neural activity is reduced, RA synthesis is stimulated, and RA signalling via RARα derepresses the translation of proteins and synergistically with the fragile X mental retardation protein allows the synthesis of Ca2+ permeable α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors that re-establish normal levels of synaptic activity. Homoeostatic synaptic plasticity underlies many cognitive processes, so its impairment due to dysregulation of RA signalling may be involved in neurodevelopmental disorders such as autism, which is also associated with FMRP. A full understanding of RA signalling control of homoeostatic synaptic plasticity may point to treatments.","PeriodicalId":16570,"journal":{"name":"Journal of molecular endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71482598","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New methods to investigate the GnRH pulse generator 研究 GnRH 脉冲发生器的新方法

IF 3.5 4区医学

Journal of molecular endocrinology Pub Date : 2023-12-01 DOI: 10.1530/jme-23-0079

Deyana Ivanova, Kevin O'Byrne

引用次数: 0