Molecular and Cellular Endocrinology最新文献

{"title":"Extragonadal function of follicle-stimulating hormone: Evidence for a role in endothelial physiology and dysfunction","authors":"Maria Santa Rocca ,&nbsp;Micaela Pannella ,&nbsp;Erva Bayraktar ,&nbsp;Saralea Marino ,&nbsp;Mario Bortolozzi ,&nbsp;Andrea Di Nisio ,&nbsp;Carlo Foresta ,&nbsp;Alberto Ferlin","doi":"10.1016/j.mce.2024.112378","DOIUrl":"10.1016/j.mce.2024.112378","url":null,"abstract":"<div><h3>Aims</h3><div>Follicle-stimulating hormone (FSH) plays a fundamental role in reproduction stimulating ovarian folliculogenesis, Sertoli cells function and spermatogenesis. However, the recent identification of FSH receptor (FSHR) also in extra-gonadal tissues has suggested that FSH activity may not be limited only to fertility regulation, with conflicting results on the possible role of FSH in endothelial cells. The aim of this study was to investigate FSH role on endothelial function in Human Umbilical Vein Endothelial Cells (HUVECs).</div></div><div><h3>Results</h3><div>Endothelial Nitric oxide synthase (<em>eNOS</em>) expression, eNOS phosphorylation and Nitric Oxide (NO) production resulted increased after the stimulation of HUVEC with recombinant human FSH (rhFSH) at 3.6x10³ ng/ml, with increasing Calcium release from intracellular stores. Furthermore, IP₃ production increased after rhFSH stimulation despite PTX treatment and NFAT1 was observed prevalently in nucleus.</div><div>We observed a statistical difference between untreated cells and cells stimulated with 0.36x10³ ng/ml and between cells stimulated with 0.36x10³ ng/ml and cells stimulated with 1.8x10³ ng/ml at 4 and 8 h by Wound healing assay, respectively. Furthermore, a higher cellular permeability was observed in stimulated cells, with atypical VE-cadherin distribution, as well as filamentous actin.</div></div><div><h3>Conclusions</h3><div>Our findings suggest that FSH at high concentrations elicits a signalling that could compromise the endothelial membrane. Indeed, VE-cadherin anomalies may severely affect the endothelial barrier, resulting in an increased membrane permeability. Although NO is an important vasodilatation factor, probably an excessive production could impact on endothelial functionality, partially explaining the increased risk of cardiovascular diseases in menopausal women and men with hypogonadism.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350240","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}

{"title":"Transmembrane and coiled-coil domain family 3 gene is a novel target of hepatic peroxisome proliferator-activated receptor γ in fatty liver disease","authors":"Daisuke Aibara,&nbsp;Ai Sakaguchi,&nbsp;Kimihiko Matsusue","doi":"10.1016/j.mce.2024.112379","DOIUrl":"10.1016/j.mce.2024.112379","url":null,"abstract":"<div><div>The peroxisome proliferator-activated receptor gamma (PPARγ) is a nuclear receptor abundantly expressed in the nonalcoholic fatty liver disease (NAFLD). In this study, we investigated the mechanism by which PPARγ regulates the transmembrane and coiled-coil domain family 3 (<em>Tmcc3</em>) gene in the liver. We found that TMCC3 is highly expressed in the fatty liver of humans and mice with NAFLD and alcoholic fatty liver disease. Three exon 1 variants (<em>Tmcc3-1a</em>, -<em>1b</em>, and -<em>1c</em>) of mouse <em>Tmcc3</em> were identified. TMCC3-1B was highly expressed in the fatty liver of type 2 diabetic <em>ob/ob</em> mice; however, this increase in expression was ameliorated by liver-specific knockout of PPARγ. Reporter assays and electrophoretic mobility shift assays showed that PPARγ positively regulates <em>Tmcc3-1b</em> and <em>-1c</em> transcription through the same PPARγ-responsive element present in the 5′-region of each <em>Tmcc3</em>. Altogether, our results indicate that <em>Tmcc3</em> is a novel PPARγ target in the fatty liver disease.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350242","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}

{"title":"Beta cell specific ZnT8 gene deficiency and resulting loss in zinc content significantly improve insulin secretion","authors":"Anthony Piro ,&nbsp;Yihan Luo ,&nbsp;Ziyi Zhang ,&nbsp;Wenyue Ye ,&nbsp;Fei Kang ,&nbsp;Li Xie ,&nbsp;Yufeng Wang ,&nbsp;Feihan F. Dai ,&nbsp;Herbert Y. Gaisano ,&nbsp;Jonathan V. Rocheleau ,&nbsp;Kacey J. Prentice ,&nbsp;Michael B. Wheeler","doi":"10.1016/j.mce.2024.112376","DOIUrl":"10.1016/j.mce.2024.112376","url":null,"abstract":"<div><div>Zinc transporter 8 (ZnT8) is highly expressed in pancreatic beta cells, localizes to insulin secretory granules (ISG), and regulates zinc content. ZnT8 gene polymorphisms have revealed a relationship between ZnT8 activity and type 2 diabetes (T2D) risk, however, the role of beta-cell ZnT8 is not well understood.</div><div>A beta cell specific ZnT8 knockout (ZnT8 BKO) mouse model was investigated. ZnT8 BKO islets showed significantly reduced ZnT8 gene expression and reduced zinc content. Compared to controls, ZnT8 BKO mice displayed significantly elevated plasma insulin levels and improved glucose tolerance following acute insulin resistance induced via S961. Glucose stimulated insulin secretion from isolated ZnT8 BKO pancreatic islets revealed enhanced insulin secretion capacity. The difference in insulin secretion between ZnT8 BKO and control islets was negated upon zinc supplementation, and the inhibitory effect of zinc on insulin secretion was confirmed in human islets.</div><div>These results indicate that the loss of ZnT8 activity and accompanying reduced cellular zinc are associated with increased insulin secretion capacity. The reduction in secreted insulin content upon zinc supplementation in ZnT8 BKO islets suggests that ISG-released zinc normally tempers insulin secretion.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142350236","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}

{"title":"High concentrations of progesterone inhibit the expression of genes related to steroid metabolism in MA-10 Leydig cells","authors":"Liel-Sarah Izichkis ,&nbsp;Audrey Basque ,&nbsp;Luc J. Martin","doi":"10.1016/j.mce.2024.112375","DOIUrl":"10.1016/j.mce.2024.112375","url":null,"abstract":"<div><div>Leydig cells are the main testosterone-producing cells in males. During androgen synthesis, cholesterol enters the mitochondria via the STAR protein and is converted into pregnenolone by the CYP11A1 enzyme. This steroid is then exported from the mitochondria to be metabolized to progesterone by the HSD3B1 enzyme in the endoplasmic reticulum. In this study, we used 3′Tag-RNA-Seq to identify progesterone-regulated genes in MA-10 Leydig cells. Our results indicate that high concentrations of progesterone (30 μM) are involved in a negative feedback loop that inhibits cAMP/PKA-dependent activation of <em>Star</em> and <em>Cyp11a1</em> expression and participate in cAMP/PKA-dependent down-regulation of genes related to the metabolism of steroid hormones. Linked to activation of the MAPK signaling pathway, endoplasmic reticulum stress and apoptosis, most of the genes encoding bZIP transcription factors are upregulated by progesterone in MA-10 Leydig cells. However, only DDIT3 protein levels are increased in response to progesterone in MA-10 Leydig cells. Like normal Leydig cells, MA-10 cells very weakly express the classical nuclear receptor for progesterone, suggesting that gene regulation by progesterone is rather mediated by one of the non-classical membrane receptors for progesterone However, current findings suggest that the inhibitory effect of progesterone on STAR protein increase in response to forskolin is not dependent on PGRMC1/2 or PAQR9. Furthermore, the increase in progesterone synthesis in response to activation of the cAMP/PKA pathway is rather inhibited by siRNA-mediated knockdown of PAQR9. Overall, this study shows that progesterone produced by Leydig cells participates in the regulation of steroidogenesis through autocrine action involving negative feedback upon activation of the cAMP/PKA pathway.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0303720724002314/pdfft?md5=49aedb0492c831ffc16384ad6fb30940&pid=1-s2.0-S0303720724002314-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291436","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}

{"title":"Liraglutide prevents body and fat mass gain in ovariectomized Wistar rats","authors":"Camila Lüdke Rossetti ,&nbsp;Iris Soares Andrade ,&nbsp;Luiz Fernando Fonte Boa ,&nbsp;Marcelo Barbosa Neves ,&nbsp;Larissa Brito Fassarella ,&nbsp;Iala Milene Bertasso ,&nbsp;Maria das Graças Coelho de Souza ,&nbsp;Eliete Bouskela ,&nbsp;Patrícia Cristina Lisboa ,&nbsp;Christina Maeda Takyia ,&nbsp;Isis Hara Trevenzoli ,&nbsp;Rodrigo Soares Fortunato ,&nbsp;Denise Pires de Carvalho","doi":"10.1016/j.mce.2024.112374","DOIUrl":"10.1016/j.mce.2024.112374","url":null,"abstract":"<div><div>Estrogens exert beneficial metabolic effects by reducing food intake and enhancing energy expenditure through both central and peripheral mechanisms. The decrease of estrogen, as occurs in ovariectomy (OVX), leads to metabolic disturbances, such as increased body weight, adipose tissue mass, basal blood glucose, and impaired glucose tolerance. These effects can be reversed by reintroducing estrogen. GLP-1 and its receptor agonists, known for their antihyperglycemic properties, also exhibit anorexigenic effects. Besides that, research indicates that GLP-1 analogs can induce metabolic changes peripherally, such as increased fatty acid oxidation and inhibited lipogenesis. Given the shared metabolic actions of GLP-1 and estrogens, we explored whether liraglutide, a GLP-1 agonist, could mitigate the metabolic effects of estrogen deficiency. We tested this hypothesis using ovariectomized rats, a model that simulates menopausal estrogen deficiency, and treated them with either liraglutide or 17β-Estradiol benzoate for 21 days. Ovariectomy resulted in elevated DPP-IV activity in both plasma and inguinal white adipose tissue (iWAT). While estrogen replacement effectively countered the DPP-IV increase in both plasma and iWAT, liraglutide only prevented the rise in iWAT DPP-IV activity. Liraglutide prevented body weight and fat mass gain after ovariectomy to the same extent as estradiol treatment. This can be explained by the lower food intake and food efficiency caused by estradiol and liraglutide. However, liraglutide was associated with increased pro-inflammatory cytokines and inflammatory cells in white adipose tissue. Further research is crucial to fully understand the potential benefits and risks of using GLP-1 receptor agonists in the context of menopause.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142291437","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}

{"title":"Nuclear receptor corepressor 1 levels differentially impact the intracellular dynamics of mutant thyroid hormone receptors associated with resistance to thyroid hormone syndrome","authors":"Yigit K. Simsek,&nbsp;H. Page Tofil,&nbsp;Matthew I. Rosenthal,&nbsp;Rochelle M. Evans,&nbsp;Caroline L. Danielski,&nbsp;Katelyn E. Beasley,&nbsp;Haytham Alsayed,&nbsp;Molly E. Shapira,&nbsp;Rebecca I. Strauss,&nbsp;Moyao Wang,&nbsp;Vincent R. Roggero,&nbsp;Lizabeth A. Allison","doi":"10.1016/j.mce.2024.112373","DOIUrl":"10.1016/j.mce.2024.112373","url":null,"abstract":"<div><p>Thyroid hormone receptor α1 (TRα1) undergoes nucleocytoplasmic shuttling and mediates gene expression in response to thyroid hormone (T3). In Resistance to Thyroid Hormone Syndrome α (RTHα), certain TRα1 mutants have higher affinity for nuclear corepressor 1 (NCoR1) and may form stable complexes that are not released in the presence of T3. Here, we examined whether NCoR1 modulates intranuclear mobility and nuclear retention of TRα1 or RTHα-associated mutants in transfected human cells, as a way of analyzing critical structural components of TRα1 and to further explore the correlation between mutations in TRα1 and aberrant intracellular trafficking. We found no significant difference in intranuclear mobility, as measured by fluorescence recovery after photobleaching, between TRα1 and select RTHα mutants, irrespective of NCoR1 expression. Nuclear-to-cytoplasmic fluorescence ratios of RTHα mutants, however, varied from TRα1 when NCoR1 was overexpressed, with a significant increase in nuclear retention for A263V and a significant decrease for A263S and R384H. In NCoR1-knockout cells, nuclear retention of A263S, A263V, P389R, A382P, C392X, and F397fs406X was significantly decreased compared to control (wild-type) cells. Luciferase reporter gene transcription mediated by TRα1 was significantly repressed by both NCoR1 overexpression and NCoR1 knockout. Most RTHα mutants showed minimal induction regardless of NCoR1 levels, but T3-mediated transcriptional activity was decreased for R384C and F397fs406X when NCoR1 was overexpressed, and also decreased for N359Y in NCoR1-knockout cells. Our results suggest a complex interaction between NCoR1 and RTHα mutants characterized by aberrant intracellular localization patterns and transcriptional activity that potentially arise from variable repressor complex stability, and may provide insight into RTHα pathogenesis on a molecular and cellular level.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0303720724002296/pdfft?md5=605eb14ee06c1bc01b9f3d2fe14e7be4&pid=1-s2.0-S0303720724002296-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242067","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}

{"title":"The adipose tissue melanocortin 3 receptor is targeted by ghrelin and leptin and may be a therapeutic target in obesity","authors":"Daniela Rosendo-Silva ,&nbsp;Eduardo Lopes ,&nbsp;Tamaeh Monteiro-Alfredo ,&nbsp;Inês Falcão-Pires ,&nbsp;Hans Eickhoff ,&nbsp;Sofia Viana ,&nbsp;Flávio Reis ,&nbsp;Ana Salomé Pires ,&nbsp;Ana Margarida Abrantes ,&nbsp;Maria Filomena Botelho ,&nbsp;Raquel Seiça ,&nbsp;Paulo Matafome","doi":"10.1016/j.mce.2024.112367","DOIUrl":"10.1016/j.mce.2024.112367","url":null,"abstract":"<div><h3>Objective</h3><p>Obesity is linked to perturbations in energy balance mechanisms, including ghrelin and leptin actions at the hypothalamic circuitry of neuropeptide Y (NPY) and melanocortin. However, information about the regulation of this system in the periphery is still scarce. Our objective was to study the regulation of the NPY/melanocortin system in the adipose tissue (AT) and evaluate its therapeutic potential for obesity and type 2 diabetes.</p></div><div><h3>Methods</h3><p>The expression of the NPY/melanocortin receptors’ levels was assessed in the visceral AT of individuals with obesity and altered metabolism. Protein levels of these receptors were evaluated in cultured adipocytes incubated with ghrelin (30 and 100 ng/mL) and leptin (1 and 10 nM) and in the AT of an animal model with a mutation in the leptin receptor (ZSF1 rat), to understand their regulation by leptin and ghrelin. The vertical sleeve gastrectomy animal model was used to evaluate the putative therapeutic potential of the NPY/melanocortin system.</p></div><div><h3>Results</h3><p>In this study, we unravelled that leptin (1 nM and 10 nM) selectively reduced the levels of NPY5R and MC3R but no other NPYR/MCRs in cultured adipocytes. In turn, acylated ghrelin (100 ng/mL) significantly increased NPY1R, but the inhibition of its receptor also abrogates MC3R levels. However, in the <em>Lepr</em>-deficient ZSF1 rat, both NPY5R and MC3R levels were reduced, along with other NPYRs and MCRs, suggesting that leptin resistance negatively affects NPY and melanocortin signalling. In human adipose tissue, we found a downregulation of genes encoding the NPY and melanocortin receptors in the visceral AT of individuals with obesity and insulin resistance, being correlated with genes regulating metabolic activity. Additionally, diabetic obese rats submitted to vertical sleeve gastrectomy showed increased levels of NPY, melanocortin, ghrelin, and leptin receptors in the AT, including MC3R, suggesting it may constitute a therapeutic target in obesity.</p></div><div><h3>Conclusions</h3><p>Our results suggest that the AT NPY/melanocortin system, particularly the MC3R, may be involved in the neuroendocrine regulation of adipocyte metabolism. Altogether, our work shows MC3R is under the control of the ghrelin/leptin duo, is reduced in patients with obesity and prediabetes, and may constitute a therapeutic target in obesity.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0303720724002235/pdfft?md5=8003c570e08e4f3b3cd002fd1ac03bbb&pid=1-s2.0-S0303720724002235-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259306","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}

{"title":"Analysis of miR-483-3p and miR-630 expression profile in pediatric adrenocortical tumors and the effect of their modulation on adrenal tumorigenesis in vitro","authors":"Carolina Alves Pereira Corrêa ,&nbsp;Augusto Faria Andrade ,&nbsp;Luciana Chain Veronez ,&nbsp;Keteryne Rodrigues da Silva ,&nbsp;Mirella Baroni ,&nbsp;Veridiana Kill Suazo ,&nbsp;Rosane de Paula Gomes Queiroz ,&nbsp;Régia Caroline Peixoto Lira ,&nbsp;Pablo Shimaoka Chagas ,&nbsp;Silvia Regina Brandalise ,&nbsp;José Andres Yunes ,&nbsp;Carlos Augusto Fernandes Molina ,&nbsp;Sonir Roberto Rauber Antonini ,&nbsp;Elvis Terci Valera ,&nbsp;Luiz Gonzaga Tone ,&nbsp;Carlos Alberto Scrideli","doi":"10.1016/j.mce.2024.112371","DOIUrl":"10.1016/j.mce.2024.112371","url":null,"abstract":"<div><p>Pediatric adrenocortical tumors (ACT) are rare aggressive neoplasms with heterogeneous prognosis. MicroRNA (miRNA) signatures have been associated with cancer diagnosis, treatment response, and outcomes of several types of cancer. However, the role played by miRNAs in pediatric ACT has been poorly explored. In this study, we have evaluated the expression of miR-483-3p and miR-630 in 67 pediatric ACT and 19 non-neoplastic adrenal samples, the effects of the modulations of these miRNAs, and their relationship with the TGF-β pathway in the H295R and H295A cell lines. Deregulation of both miRNAs was related to survival and disease advanced stages and hence to patients’ prognosis. Moreover, modified miR-483-3p and miR-630 <em>in vitro</em> expression decreased cell viability and colony formation capacity, changed how some genes of the TGF-β pathway, such as <em>TGFBR1</em>, <em>TGFBR2</em>, and <em>SMAD7</em>, are expressed, and altered Smad3, pSmad3, Smad 2/3, N-cadherin, and Vimentin protein expression. Besides that, when inhibition of the TGF-β pathway was combined with miR-630 overexpression or miR-483-3p silencing, cell viability and colony formation capacity decreased, and protein expression in the TGF-β pathway changed. Together, the data indicate that both miRNAs participate in the TGF-β pathway and are therefore potential markers for predicting the prognosis of patients with pediatric ACT.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270785","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}

{"title":"Sex hormones and life histories: An evolutionary perspective","authors":"Gustavo M. Somoza, Vance L. Trudeau","doi":"10.1016/j.mce.2024.112372","DOIUrl":"https://doi.org/10.1016/j.mce.2024.112372","url":null,"abstract":"","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":4.1,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142259305","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}

{"title":"Hyperthyroidism keeps immunoglobulin levels but reduces milk fat and CD11b/c+ cells on early lactation","authors":"María Belén Sánchez ,&nbsp;María Cecilia Michel Lara ,&nbsp;Flavia Judith Neira ,&nbsp;Claudio Rodríguez-Camejo ,&nbsp;Juan Manuel Ríos ,&nbsp;Luciana Belén Viruel ,&nbsp;María Tamara Moreno-Sosa ,&nbsp;Elisa Olivia Pietrobon ,&nbsp;Marta Soaje ,&nbsp;Graciela Alma Jahn ,&nbsp;Ana Hernández ,&nbsp;Susana Ruth Valdez ,&nbsp;Juan Pablo Mackern-Oberti","doi":"10.1016/j.mce.2024.112370","DOIUrl":"10.1016/j.mce.2024.112370","url":null,"abstract":"<div><p>Thyroid hormones influence mammary gland differentiation and lactation by binding to thyroid hormone receptors. Hyperthyroidism disrupts pregnancy and lactation, affecting offspring growth and milk production. Despite maternal milk is a vital source of bioactive compounds and nutrients for newborns, it is unclear whether hyperthyroidism alters its composition, mainly immune factors. Therefore, our work aimed to evaluate the influence of hyperthyroidism on milk quality and immunological parameters during early lactation. Twelve-week-old female Wistar rats received daily injections of 0,25 mg/kg T₄ (HyperT, n = 20) or vehicle (control, n = 19) starting 8 days before mating and continuing throughout pregnancy. Rats were euthanized on day 2 of lactation for analyzing the impact of hyperthyroidism on mammary gland, serum and milk samples. HyperT pups exhibited reduced weight, length and head circumference with altered serum hormones, glucose and albumin levels. HyperT mammary gland analysis revealed structural changes, including decreased alveolar area, adipose tissue, increased connective tissue and reduced epithelial elongation, accompanied by decreased TRβ1 RNA expression. HyperT milk displayed lower caloric value and fat concentration. HyperT animals exhibited altered milk immune cell counts, displaying increased numbers of CD45⁺ and CD3⁺ cells and decreased CD11b/c⁺ cells without changes on milk and serum IgA, IgG and IgG2a levels. In summary, we have demonstrated that hyperthyroidism affects mammary gland morphology, disrupts pup development and alters biochemical and immunological parameters. Our findings highlight the impact of maternal hyperthyroidism on offspring early development and milk immune composition, underscoring the importance of thyroid function in maternal and neonatal immune health.</p></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142270784","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}