Endocrinology最新文献_第9页

GDF15 Knockout Does Not Substantially Impact Perinatal Body Weight or Neonatal Outcomes in Mice. GDF15 基因敲除不会对小鼠围产期体重或新生儿预后产生重大影响。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae143

Molly C Mulcahy, Noura El Habbal, JeAnna R Redd, Haijing Sun, Brigid E Gregg, Dave Bridges

引用次数: 0

Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice. 靶向删除成纤维细胞生长因子-23可挽救雌性小鼠饮食诱发肥胖的代谢失调。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae141

Min Young Park, Chia-Ling Tu, Luce Perie, Narendra Verma, Tamires Duarte Afonso Serdan, Farnaz Shamsi, Sue Shapses, Sean Heffron, Begona Gamallo-Lana, Adam C Mar, José O Alemán, Elisabetta Mueller, Wenhan Chang, Despina Sitara

{"title":"Targeted Deletion of Fibroblast Growth Factor 23 Rescues Metabolic Dysregulation of Diet-induced Obesity in Female Mice.","authors":"Min Young Park, Chia-Ling Tu, Luce Perie, Narendra Verma, Tamires Duarte Afonso Serdan, Farnaz Shamsi, Sue Shapses, Sean Heffron, Begona Gamallo-Lana, Adam C Mar, José O Alemán, Elisabetta Mueller, Wenhan Chang, Despina Sitara","doi":"10.1210/endocr/bqae141","DOIUrl":"10.1210/endocr/bqae141","url":null,"abstract":"Fibroblast growth factor 23 (FGF23) is a bone-secreted protein widely recognized as a critical regulator of skeletal and mineral metabolism. However, little is known about the nonskeletal production of FGF23 and its role in tissues other than bone. Growing evidence indicates that circulating FGF23 levels rise with a high-fat diet (HFD) and they are positively correlated with body mass index (BMI) in humans. In the present study, we show for the first time that increased circulating FGF23 levels in obese humans correlate with increased expression of adipose Fgf23 and both positively correlate with BMI. To understand the role of adipose-derived Fgf23, we generated adipocyte-specific Fgf23 knockout mice (AdipoqFgf23Δfl/Δfl) using the adiponectin-Cre driver, which targets mature white, beige, and brown adipocytes. Our data show that targeted ablation of Fgf23 in adipocytes prevents HFD-fed female mice from gaining body weight and fat mass while preserving lean mass but has no effect on male mice, indicating the presence of sexual dimorphism. These effects are observed in the absence of changes in food and energy intake. Adipose Fgf23 inactivation also prevents dyslipidemia, hyperglycemia, and hepatic steatosis in female mice. Moreover, these changes are associated with decreased respiratory exchange ratio and increased brown fat Ucp1 expression in knockout mice compared to HFD-fed control mice (Fgf23fl/fl). In conclusion, this is the first study highlighting that targeted inactivation of Fgf23 is a promising therapeutic strategy for weight loss and lean mass preservation in humans.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497369","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Characterization and Regulation of the Neonatal Growth Hormone Surge. 新生儿生长激素激增的特征和调节。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae140

Daniela O Gusmao, Ligia M M de Sousa, Maria E de Sousa, Stephanie J R Rusew, Edward O List, John J Kopchick, Andre F Gomes, Ana C Campideli-Santana, Raphael E Szawka, Jose Donato

{"title":"Characterization and Regulation of the Neonatal Growth Hormone Surge.","authors":"Daniela O Gusmao, Ligia M M de Sousa, Maria E de Sousa, Stephanie J R Rusew, Edward O List, John J Kopchick, Andre F Gomes, Ana C Campideli-Santana, Raphael E Szawka, Jose Donato","doi":"10.1210/endocr/bqae140","DOIUrl":"10.1210/endocr/bqae140","url":null,"abstract":"High neonatal growth hormone (GH) secretion has been described in several species. However, the neuroendocrine mechanisms behind this surge remain unknown. Thus, the pattern of postnatal GH secretion was investigated in mice and rats. Blood GH levels were very high on postnatal day (P)1 and progressively decreased until near zero by P17 in C57BL/6 mice without sex differences. This pattern was similar to that observed in rats, except that female rats showed higher GH levels on P1 than males. In comparison, follicle-stimulating hormone exhibited higher secretion in females during the first 3 weeks of life. Hypothalamic Sst mRNA and somatostatin neuroendocrine terminals in the median eminence were higher in P20/P21 mice than in newborns. Knockout mice for GH-releasing hormone (GHRH) receptor showed no GH surge, whereas knockdown mice for the Sst gene displayed increased neonatal GH peak. Leptin deficiency caused only minor effects on early-life GH secretion. GH receptor ablation in neurons or the entire body did not affect neonatal GH secretion, but the subsequent reduction in blood GH levels was attenuated or prevented by these genetic manipulations, respectively. This phenotype was also observed in knockout mice for the insulin-like growth factor-1 (IGF-1) receptor in GHRH neurons. Moreover, glucose-induced hyperglycemia overstimulated GH secretion in neonatal mice. In conclusion, GH surge in the first days of life is not regulated by negative feedback loops. However, neonatal GH secretion requires GHRH receptor, and is modulated by somatostatin and blood glucose levels, suggesting that this surge is controlled by hypothalamic-pituitary communication.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11544317/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Long-term, Dynamic Remodelling of the Corticotroph Transcriptome and Excitability After a Period of Chronic Stress. 长期慢性应激后皮质转录组和兴奋性的长期动态重塑。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae139

Peter J Duncan, Nicola Romanò, Sooraj V Nair, Heather McClafferty, Paul Le Tissier, Michael J Shipston

{"title":"Long-term, Dynamic Remodelling of the Corticotroph Transcriptome and Excitability After a Period of Chronic Stress.","authors":"Peter J Duncan, Nicola Romanò, Sooraj V Nair, Heather McClafferty, Paul Le Tissier, Michael J Shipston","doi":"10.1210/endocr/bqae139","DOIUrl":"10.1210/endocr/bqae139","url":null,"abstract":"Chronic stress results in long-term dynamic changes at multiple levels of the hypothalamic-pituitary-adrenal (HPA) axis resulting in stress axis dysregulation with long-term impacts on human and animal health. However, the underlying mechanisms and dynamics of altered of HPA axis function, in particular at the level of pituitary corticotrophs, during a period of chronic stress and in the weeks after its cessation (defined as \"recovery\") are very poorly understood. Here, we address the fundamental question of how a period of chronic stress results in altered anterior pituitary corticotroph function and whether this persists in recovery, as well as the transcriptomic changes underlying this. We demonstrate that, in mice, spontaneous and corticotrophin-releasing hormone-stimulated electrical excitability of corticotrophs, essential for ACTH secretion, is suppressed for weeks to months of recovery following a period of chronic stress. Surprisingly, there are only modest changes in the corticotroph transcriptome during the period of stress, but major alterations occur in recovery. Importantly, although transcriptional changes for a large proportion of mRNAs follow the time course suppression of corticotroph excitability, many other genes display highly dynamic transcriptional changes with distinct time courses throughout recovery. Taken together, this suggests that chronic stress results in complex dynamic transcriptional and functional changes in corticotroph physiology, which are highly dynamic for weeks following cessation of chronic stress. These insights provide a fundamental new framework to further understand underlying molecular mechanisms as well approaches to both diagnosis and treatment of stress-related dysfunction of the HPA axis.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

LCoRL Regulates Growth and Metabolism. LCoRL 可调节生长和新陈代谢。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae146

Steven C Wyler, Surbhi Gahlot, Lara Bideyan, Cecilia Yip, Jasmine Dushime, Bandy Chen, Jenny J Lee, Arely Tinajero, Chelsea Limboy, Staci Bordash, Samuel R Heaselgrave, Tammy-Nhu Nguyen, Syann Lee, Angie Bookout, Loise Lantier, John L Fowlkes, Young-Jai You, Teppei Fujikawa, Joel K Elmquist

{"title":"LCoRL Regulates Growth and Metabolism.","authors":"Steven C Wyler, Surbhi Gahlot, Lara Bideyan, Cecilia Yip, Jasmine Dushime, Bandy Chen, Jenny J Lee, Arely Tinajero, Chelsea Limboy, Staci Bordash, Samuel R Heaselgrave, Tammy-Nhu Nguyen, Syann Lee, Angie Bookout, Loise Lantier, John L Fowlkes, Young-Jai You, Teppei Fujikawa, Joel K Elmquist","doi":"10.1210/endocr/bqae146","DOIUrl":"10.1210/endocr/bqae146","url":null,"abstract":"Genome-wide association studies (GWAS) in humans and livestock have identified genes associated with metabolic traits. However, the causality of many of these genes on metabolic homeostasis is largely unclear due to a lack of detailed functional analyses. Here we report ligand-dependent corepressor-like (LCoRL) as a metabolic regulator for body weight and glucose homeostasis. Although GWAS data show that LCoRL is strongly associated with body size, glucose homeostasis, and other metabolic traits in humans and livestock, functional investigations had not been performed. We generated Lcorl knockout mice (Lcorl-/-) and characterized the metabolic traits. We found that Lcorl-/- pups are born smaller than the wild-type (WT) littermates before reaching normal weight by 7 to 9 weeks of age. While aging, Lcorl-/- mice remain lean compared to WT mice, which is associated with a decrease in daily food intake. Glucose tolerance and insulin sensitivity are improved in Lcorl-/- mice. Mechanistically, this stunted growth is linked to a reduction of circulating levels of IGF-1. The expression of the genes downstream of GH signaling and the genes involved in glucose and lipid metabolism are altered in the liver of Lcorl-/- mice. Furthermore, Lcorl-/- mice are protected against a high-fat diet challenge and show reduced exercise capacity in an exercise stress test. Collectively, our results are congruent with many of the metabolic parameters linked to the Lcorl locus as reported in GWAS in humans and livestock.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11538781/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142521421","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells. 在小鼠垂体发育和成熟激素分泌细胞中表达的长非编码 RNA。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae147

Michelle Lynn Brinkmeier, Akima Semone George, Leonard Yan Ming Cheung, Ryan Edward Mills, Philippa Melamed, Sally Ann Camper

{"title":"Long Noncoding RNAs Expressed in Mouse Pituitary Development and Mature Hormone-Producing Cells.","authors":"Michelle Lynn Brinkmeier, Akima Semone George, Leonard Yan Ming Cheung, Ryan Edward Mills, Philippa Melamed, Sally Ann Camper","doi":"10.1210/endocr/bqae147","DOIUrl":"10.1210/endocr/bqae147","url":null,"abstract":"Mammalian genomes contain thousands of genes for long noncoding RNA (lncRNAs), some of which have been shown to affect protein coding gene expression through diverse mechanisms. The lncRNA transcripts are longer than 200 nucleotides and are often capped, spliced, and polyadenylated, but not translated into protein. Nuclear lncRNAs can modify chromatin structure and transcription in trans or cis by interacting with the DNA, forming R-loops, and recruiting regulatory proteins. Not much is known about the role of lncRNA in pituitary gland differentiation and function. We mined transcriptome data from mouse pituitary glands collected at embryonic days 12.5 and 14.5 and identified over 200 different lncRNA transcripts. To develop a research resource for the study of lncRNA, we used pituitary cre transgenes to tag pituitary cell types in adult mice with fluorescent markers, and enriched for thyrotropes, gonadotropes, and somatotropes using fluorescence-activated cell sorting. We determined the transcriptome of each cell population using RNA sequencing and mined the data for lncRNA. We detected hundreds of lncRNAs in adult pituitary cells; a few were located immediately nearby genes that encode pituitary hormones or lineage-specific transcription factors. The location of these lncRNAs suggests the possibility of a cis-acting regulatory role in pituitary development or function, and we observe coordinated expression of 2 of them with their putative target genes in transgenic mice. This research resource sets the foundation for examining the actions of lncRNAs on their putative target genes and determining whether they have roles during development and in response to physiological demand.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565238/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142564016","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

GnRH-Gonadotropes Interactions Revealed by Pituitary Single-cell Transcriptomics in Zebrafish. 斑马鱼垂体单细胞转录组学揭示的促性腺激素释放激素与促性腺激素之间的相互作用

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae151

Sakura Tanaka, Yang Yu, Berta Levavi-Sivan, Nilli Zmora, Yonathan Zohar

{"title":"GnRH-Gonadotropes Interactions Revealed by Pituitary Single-cell Transcriptomics in Zebrafish.","authors":"Sakura Tanaka, Yang Yu, Berta Levavi-Sivan, Nilli Zmora, Yonathan Zohar","doi":"10.1210/endocr/bqae151","DOIUrl":"10.1210/endocr/bqae151","url":null,"abstract":"GnRH governs reproduction by regulating pituitary gonadotropins. Unlike most vertebrates, gnrh-/- zebrafish are fertile. To elucidate the role of the hypophysiotropic-Gnrh3 and other mechanisms regulating pituitary gonadotropes, we profiled the gene expression of all individual pituitary cells of wild-type and gnrh3-/- adult female zebrafish. The single-cell RNA sequencing showed that LH and FSH gonadotropes express the 2 gonadotropin beta subunits with a ratio of 140:1 (lhb:fshb) and 4:1 (fshb:lhb), respectively. Lh gonadotropes predominantly express genes encoding receptors for GnRH (gnrhr2), thyroid hormone, estrogen, and steroidogenic factor 1. No GnRH receptor transcript was enriched in FSH gonadotropes. Instead, cholecystokinin receptor-b and galanin receptor-1b transcripts were enriched in these cells. The loss of the Gnrh3 gene in gnrh3-/- zebrafish resulted in downregulation of fshb in LH gonadotropes and upregulation of pituitary hormones like TSH, GH, prolactin, and proopiomelanocortin-a. Likewise, targeted chemogenetic ablation of Gnrh3 neurons led to a decrease in the number of fshb+, lhb + and fshb+/lhb + cells. Our studies suggest that Gnrh3 directly acts on LH gonadotropes through Gnrhr2, but the outcome of this interaction is still unknown. Gnrh3 also regulates fshb expression in both gonadotropes, most likely via a non-GnRH receptor route. Altogether, while LH secretion and synthesis are likely regulated in a GnRH-independent manner, Gnrh3 seems to play a role in the cellular organization of the pituitary. Moreover, the coexpression of lhb and fshb in both gonadotropes provides a possible explanation as to why gnrh3-/- zebrafish are fertile.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565244/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581764","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Correction to: "Androgen Receptor Regulation of Local Growth Hormone in Prostate Cancer Cells". 更正："雄激素受体对前列腺癌细胞中局部生长激素的调控》。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae145

引用次数: 0

Nonylphenol and Cetyl Alcohol Polyethoxylates Disrupt Thyroid Hormone Receptor Signaling to Disrupt Metabolic Health. 壬基酚和十六烷基酚聚氧乙烯醚会干扰甲状腺激素受体信号传递，从而破坏代谢健康。

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae149

Roxanne Bérubé, Brooklynn Murray, Thomas A Kocarek, Katherine Gurdziel, Christopher D Kassotis

{"title":"Nonylphenol and Cetyl Alcohol Polyethoxylates Disrupt Thyroid Hormone Receptor Signaling to Disrupt Metabolic Health.","authors":"Roxanne Bérubé, Brooklynn Murray, Thomas A Kocarek, Katherine Gurdziel, Christopher D Kassotis","doi":"10.1210/endocr/bqae149","DOIUrl":"10.1210/endocr/bqae149","url":null,"abstract":"Surfactants are molecules with both hydrophobic and hydrophilic structural groups that adsorb at the air-water or oil-water interface and serve to decrease the surface tension. Surfactants combine to form micelles that surround and break down or remove oils, making them ideal for detergents and cleaners. Two of the most important classes of nonionic surfactants are alkylphenol ethoxylates (APEOs) and alcohol ethoxylates (AEOs). APEOs and AEOs are high production-volume chemicals that are used for many industrial and residential purposes, including laundry detergents, hard-surface cleaners, paints, and pesticide adjuvants. Commensurate with better appreciation of the toxicity of APEOs and the base alkylphenols, use of AEOs has increased, and both sets of compounds are now ubiquitous environmental contaminants. We recently demonstrated that diverse APEOs and AEOs induce triglyceride accumulation and/or preadipocyte proliferation in vitro. Both sets of contaminants have also been demonstrated as obesogenic and metabolism-disrupting in a developmental exposure zebrafish model. While these metabolic health effects are consistent across models and species, the mechanisms underlying these effects are less clear. This study sought to evaluate causal mechanisms through reporter gene assays, relative binding affinity assays, coexposure experiments, and use of both human cell and zebrafish models. We report that antagonism of thyroid hormone receptor signaling appears to mediate at least a portion of the polyethoxylate-induced metabolic health effects. These results suggest further evaluation is needed, given the ubiquitous environmental presence of these thyroid-disrupting contaminants and reproducible effects in human cell models and vertebrate animals.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11574291/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142575825","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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

Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels. 产前母体应激通过升高糖皮质激素水平抑制胚胎神经发生

IF 3.8 3区医学

Endocrinology Pub Date : 2024-10-30 DOI: 10.1210/endocr/bqae150

Shujie Xu, Junzhu Shi, Yao Shen, Xianlong Chen, Ghazal Pourbozorg, Guang Wang, Xuesong Yang, Xin Cheng

{"title":"Prenatal Maternal Stress Suppresses Embryonic Neurogenesis via Elevated Glucocorticoid Levels.","authors":"Shujie Xu, Junzhu Shi, Yao Shen, Xianlong Chen, Ghazal Pourbozorg, Guang Wang, Xuesong Yang, Xin Cheng","doi":"10.1210/endocr/bqae150","DOIUrl":"10.1210/endocr/bqae150","url":null,"abstract":"Although it is known that prenatal maternal stress (PNMS) has a negative influence on nervous system development in offspring, there is no conclusive evidence clarifying its impact on early neurogenesis during development. In this study, we established a chick embryo model to investigate how PNMS affects early neurogenesis by mimicking an intrauterine environment with elevated dexamethasone levels. The results showed that dexamethasone-mimicked PNMS significantly suppressed the development of gastrula embryos and increased the risks of neural tube defects and cranial deformity. Using immunofluorescence staining and Western blots to evaluate the expression levels of pHIS3 and PCNA/Sox2, we found that PNMS significantly inhibited the proliferation of neural progenitor cells and that the downregulation of TGF-β signaling pathway might be responsible for the inhibition. Furthermore, immunofluorescence staining and Western blots manifested that PNMS could suppress the differentiation of neural progenitor cells to neuronal lineages, but promote them to transform into neuroglial cells, which might be due to the restriction of expressions of key genes (BMP4, SHH, Wnt3a, Slug, and Msx1) related to neural differentiation. In summary, our data reveal that PNMS dramatically impacts the earliest stages of neural development, thereby greatly increasing the risk of physical and mental health problems in childhood or adulthood.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142581785","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"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