Endocrinology最新文献_第5页

Fifty Years of Support From the NIDDK for a Pioneer in Thyroid Research. NIDDK五十年来对甲状腺研究先驱的支持。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf060

Antonio C Bianco

引用次数: 0

Insl3-iCre Mouse Line: A Novel Effective Tool for Targeting Leydig Cells to Study Their Development and Function. Insl3-iCre小鼠系：研究间质细胞发育和功能的新有效工具

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf048

Vassilios Papadopoulos

引用次数: 0

KNDy Neurons and the Control of the Gonadotropic Axis in the Midgestation Fetal Sheep. 妊娠中期胎羊KNDy神经元与促性腺激素轴的调控。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf049

Rebecka Amodei, Sonnet S Jonker, Evelyn Lazen, Casey C Nestor, Charles T Estill, Charles E Roselli

{"title":"KNDy Neurons and the Control of the Gonadotropic Axis in the Midgestation Fetal Sheep.","authors":"Rebecka Amodei, Sonnet S Jonker, Evelyn Lazen, Casey C Nestor, Charles T Estill, Charles E Roselli","doi":"10.1210/endocr/bqaf049","DOIUrl":"10.1210/endocr/bqaf049","url":null,"abstract":"KNDy neurons, located in the hypothalamic arcuate nucleus, coexpress kisspeptin (Kiss), neurokinin B, and dynorphin and play a crucial role in regulating GnRH/LH secretion in midgestation sheep fetuses. We hypothesize that KNDy-GnRH signaling is established during midgestation, with negative feedback acting through KNDy neurons regulating testosterone levels needed for brain masculinization in male fetuses. We used immunofluorescence histochemistry to assess the effect of chemical castration with the GnRH antagonist degarelix on arcuate KNDy neurons in fetal sheep. Fluorescent in situ hybridization demonstrated the presence of steroid receptors in untreated midgestation fetal kisspeptin neurons. Additionally, unanesthetized cannulated midgestation fetal sheep were used to examine the effects of KNDy peptides on LH secretion and characterize receptor specificity. Treatment of male lamb fetuses with degarelix on day 62 of gestation resulted in significantly decreased plasma LH and testosterone concentrations (P < .05), accompanied by a significant increase in arcuate Kiss neurons (P < .05). In unanesthetized cannulated fetuses, bolus administration of KP-10 (a Kiss receptor agonist) and senktide (NK3 receptor agonist) elicited robust LH release within 15 minutes. Pretreatment with the NK3 receptor antagonist SB222200 blocked the LH response to senktide, whereas P271 (Kiss receptor antagonist) did not affect basal LH or block the LH response to KP-10. Blocking κ-opiate receptor with PF4455242 significantly increased LH release. These results support the hypothesis that KNDy neurons regulate GnRH and gonadotropin secretion in midgestation sheep fetuses, acting as targets for negative feedback to maintain a stable androgen environment crucial for brain masculinization.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143572571","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

Lipotoxicity Induces β-cell Small Extracellular Vesicle-Mediated β-cell Dysfunction in Male Mice. 脂肪毒性诱导β细胞细胞外小泡介导的雄性小鼠β细胞功能障碍。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf067

Abhishek Roy, Alexandra Hoff, Tracy K Her, Gallage Ariyaratne, Roberto-León Gutiérrez, M H D Noor Tahawi, Kamalnath Sankaran Rajagopalan, Matthew R Brown, Kazuno Omori, Sean Lewis-Brinkman, Thanh Nguyen, Alondra Soto-González, Quinn P Peterson, Aleksey V Matveyenko, Naureen Javeed

{"title":"Lipotoxicity Induces β-cell Small Extracellular Vesicle-Mediated β-cell Dysfunction in Male Mice.","authors":"Abhishek Roy, Alexandra Hoff, Tracy K Her, Gallage Ariyaratne, Roberto-León Gutiérrez, M H D Noor Tahawi, Kamalnath Sankaran Rajagopalan, Matthew R Brown, Kazuno Omori, Sean Lewis-Brinkman, Thanh Nguyen, Alondra Soto-González, Quinn P Peterson, Aleksey V Matveyenko, Naureen Javeed","doi":"10.1210/endocr/bqaf067","DOIUrl":"10.1210/endocr/bqaf067","url":null,"abstract":"Chronically elevated circulating excess free fatty acids (ie, lipotoxicity) is a pathological process implicated in several metabolic disorders, including obesity-driven type 2 diabetes (T2D). Lipotoxicity exerts detrimental effects on pancreatic islet β-cells by reducing glucose-stimulated insulin secretion (GSIS), altering β-cell transcriptional identity, and promoting apoptosis. While β-cell-derived small extracellular vesicles (sEV) have been shown to contribute to β-cell failure in T2D, their specific role in lipotoxicity-mediated β-cell failure remains to be elucidated. In this work, we demonstrate that lipotoxicity enhances the release of sEVs from β-cells, which exhibit altered proteomic and lipidomic profiles. These palmitate (PAL)-exposed extracellular vesicles (EVs) induce β-cell dysfunction in healthy mouse and human islets and trigger significant islet transcriptional changes, including the upregulation of genes associated with the TGFβ/Smad3 pathway, as noted by RNA sequencing. Importantly, pharmacological inhibition of the TGFβI/II receptor improved PAL EV-induced β-cell dysfunction, underscoring their involvement in activating the TGFβ/Smad3 pathway during this process. We have comprehensively characterized lipotoxic β-cell sEVs and implicated their role in inducing β-cell functional failure in T2D. These findings highlight potential avenues for therapeutic interventions targeting sEV-mediated pathways to preserve β-cell health in metabolic disorders.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779394","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

FVB But Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter. 携带Thr92Ala-Dio2多态性的FVB而非B6小鼠有甲状腺激素生成障碍和甲状腺肿。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf046

Alice Batistuzzo, Xiaohan Zhang, Barbara M L C Bocco, Elizabeth A McAninch, Federico Salas-Lucia, Miriam O Ribeiro, Peter Arvan, Antonio C Bianco, Tatiana L Fonseca

{"title":"FVB But Not B6 Mice Carrying the Thr92Ala-Dio2 Polymorphism Have Impaired Thyroid Hormonogenesis and Goiter.","authors":"Alice Batistuzzo, Xiaohan Zhang, Barbara M L C Bocco, Elizabeth A McAninch, Federico Salas-Lucia, Miriam O Ribeiro, Peter Arvan, Antonio C Bianco, Tatiana L Fonseca","doi":"10.1210/endocr/bqaf046","DOIUrl":"10.1210/endocr/bqaf046","url":null,"abstract":"The Thr92Ala-Dio2 polymorphism is prevalent worldwide, with about 50% of the population carrying at least 1 allele. The Ala92-Dio2 allele encodes a less active type 2 deiodinase enzyme and has been associated with neurodegenerative diseases, hypertension, and insulin resistance. To understand why its phenotypic effects are variable across different populations, in this study we examined the impact of genetic background on the Thr92Ala-Dio2 polymorphism. We focused on the thyroid gland of 2 genetically distant mouse strains, the C57BL/6J (B6) and the FVB/N (FVB). While the B6-Ala92-Dio2 mice have no meaningful phenotype, the FVB-Ala92-Dio2 exhibit a goiter (about 2.3-fold heavier thyroid) with an about 1.7-fold enlarged thyroid follicular area and impaired hormonogenesis with reduced thyroglobulin content of T4 and T3, 35% to 50% lower serum T4, and about 3-fold elevated serum TSH levels. Notably, the FVB-Ala92-Dio2 thyroid glands showed transcriptional evidence of endoplasmic reticulum stress, unfolded protein response, autophagy, and apoptosis. Female FVB-Ala92-Dio2 mice exhibited a more pronounced thyroid phenotype than males. These findings underscore the critical role of genetic background in modulating the phenotype outcomes of the Thr92Ala-Dio2 polymorphism and highlight its potential implications for understanding variable disease susceptibility in human populations.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11932088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630071","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

Ovarian-Specific Cyp17A1 Overexpression in Female Mice: A Novel Model of Endogenous Testosterone Excess. 雌性小鼠卵巢特异性Cyp17A1过表达：内源性睾酮过量的新模型。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf071

Serene Joseph, Vaibhave Ubba, Zhiqiang Wang, Mingxiao Feng, Milan K dSilva, Sofia Suero, Danielle Waheed, Nathaniel W Snyder, Xiaofeng Yang, Hong Wang, JoAnne S Richards, CheMyong J Ko, Sheng Wu

{"title":"Ovarian-Specific Cyp17A1 Overexpression in Female Mice: A Novel Model of Endogenous Testosterone Excess.","authors":"Serene Joseph, Vaibhave Ubba, Zhiqiang Wang, Mingxiao Feng, Milan K dSilva, Sofia Suero, Danielle Waheed, Nathaniel W Snyder, Xiaofeng Yang, Hong Wang, JoAnne S Richards, CheMyong J Ko, Sheng Wu","doi":"10.1210/endocr/bqaf071","DOIUrl":"https://doi.org/10.1210/endocr/bqaf071","url":null,"abstract":"Excessive androgen levels can severely affect female health. However, most existing models of androgen excess rely on exogenous androgen administration, which does not fully capture the effect of elevated local ovarian testosterone on reproductive and metabolic functions. Here, we report the development of a novel hyperandrogenic mouse model, Cyp17TM-625, generated by combining CRISPR-Cas9 and a Tet-On doxycycline system to induce Cyp17A1 overexpression in ovarian theca-interstitial cells. As a result, Cyp17TM-625 mice exhibited significantly elevated Cyp17A1 messenger RNA and protein levels, accompanied by increased testosterone concentrations without alterations in basal levels of estradiol, progesterone, luteinizing hormone, or follicle-stimulating hormone. These mice demonstrated subfertility, evident by smaller and fewer litters, prolonged estrous cycles, and an increased number of unhealthy follicles with abnormally shaped oocytes. Despite these marked reproductive changes, body weight and glucose homeostasis remained comparable to Con-625 mice. Notably, withdrawal of doxycycline reversed testosterone overexpression and restored fertility over time. This model recapitulates reproductive dysfunction but not the metabolic disturbances, commonly observed in exogenous androgen models. The Cyp17TM-625 mouse line is a unique model for investigating the effects of local excess androgens on ovarian function. It also serves as a valuable tool for studying fertility restoration following the withdrawal of testosterone.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":"166 5","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143970490","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

Sex and Time of Day Alter the Interactions Between Hypothalamic Glia and the Neural Circuits Controlling Reproduction. 性别和时间会改变下丘脑胶质细胞和控制生殖的神经回路之间的相互作用。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf057

Chrystian D Phillips, R Anthony DeFazio, Suzanne M Moenter

{"title":"Sex and Time of Day Alter the Interactions Between Hypothalamic Glia and the Neural Circuits Controlling Reproduction.","authors":"Chrystian D Phillips, R Anthony DeFazio, Suzanne M Moenter","doi":"10.1210/endocr/bqaf057","DOIUrl":"10.1210/endocr/bqaf057","url":null,"abstract":"An upstream network, including glia and arcuate nucleus (ARC) kisspeptin neurons, controls hormone secretion from preoptic area (POA) gonadotropin-releasing hormone (GnRH) neurons, which form the final common pathway for the central control of fertility. In males, chemogenetic activation of Gq-mediated signaling in POA glia activated GnRH neurons and downstream luteinizing hormone (LH) release, while chemogenetic activation of ARC glia had no effect on ARC kisspeptin neurons. We characterized sex differences and time-of-day effects in these critical circuits to understand their effects on reproduction. Chemogenetic activation of glial fibrillary acidic protein (GFAP)-expressing cells increased intracellular calcium concentrations regardless of sex, brain region, or time of day. Activation of POA glia or treatment with the gliotransmitter analog dimethyl prostaglandin E2 (dmPGE2) increased GnRH neuron firing rate, and these responses were dependent upon sex and time of day. In contrast, ARC kisspeptin neuron firing rate was unresponsive to ARC glia activation or dmPGE2 regardless of sex or time of day. POA glial activation increased LH levels in males and females but the response in males was more rapid. ARC glia activation had no effect on LH in females and the response in males was delayed compared to POA glia activation. A similar LH response persisted after ARC kisspeptin neuron ablation, suggesting it is not mediated by those neurons. GnRH neurons, rather than arcuate kisspeptin neurons, are thus the main target of glial regulation of reproductive neuroendocrine output and this regulation is dependent on sex and time of day.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11968336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143662898","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

Primordial Follicle Survival and Changes in Ovarian Vasculature May Be Independently Regulated During Chemotherapy. 原始卵泡存活和卵巢脉管系统的变化可能在化疗期间独立调节。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf059

Wonmi So, Rosemary Dong, Donghee Lee, Amirhossein Abazarikia, Bryan T Hackfort, Andrea S Cupp, So-Youn Kim

{"title":"Primordial Follicle Survival and Changes in Ovarian Vasculature May Be Independently Regulated During Chemotherapy.","authors":"Wonmi So, Rosemary Dong, Donghee Lee, Amirhossein Abazarikia, Bryan T Hackfort, Andrea S Cupp, So-Youn Kim","doi":"10.1210/endocr/bqaf059","DOIUrl":"10.1210/endocr/bqaf059","url":null,"abstract":"Chemotherapeutic agents induce irreversible gonadotoxic side effects, resulting in endocrine dysfunction and infertility in female cancer survivors. In the current study, we investigated strategies to protect ovarian function from chemotherapy-induced toxicity by evaluating the effects of cisplatin, doxorubicin, or cyclophosphamide on ovarian vasculature and primordial follicle survival. This investigation was conducted using adult CD-1, PDs 5-7 CD-1, and oocyte-specific Trp63 conditional knockout (Trp63 cKO) mice that demonstrated primordial follicles survived following chemotherapy. In control ovaries, vasculature typically surrounds primordial and primary follicles, is in the theca layer as secondary follicles develop, and is distributed among stromal cells. Our findings revealed that the expression pattern of CD31/PECAM-1 (platelet endothelial adhesion molecule-1) was significantly altered in ovaries treated with chemotherapeutic agents compared with controls. The data demonstrate that these agents not only caused the loss of ovarian follicles but also damaged the ovarian vasculature. Using Trp63 cKO mice and CK2II, an inhibitor of checkpoint kinase 2, we demonstrated that vascular damage can occur independently of primordial follicle loss, and VEGFA165 was unable to prevent either outcome. This indicates that the mechanisms governing the death of primordial follicles and vascular damage may not directly affect each other. Long-term ex vivo culture and in vivo experiments demonstrated the ability of ovarian vasculature to recover from cisplatin-induced damage. In conclusion, our study suggests that ovarian follicle survival and vascular integrity may be independently regulated as independent processes, governed by distinct signaling pathway or mechanisms.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006718/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143729166","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

Early Embryo Development: What Does Daddy Do? 早期胚胎发育：爸爸做什么？

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf065

Rossella Cannarella, Roberto Curto, Rosita A Condorelli, Sandro La Vignera, Aldo E Calogero

{"title":"Early Embryo Development: What Does Daddy Do?","authors":"Rossella Cannarella, Roberto Curto, Rosita A Condorelli, Sandro La Vignera, Aldo E Calogero","doi":"10.1210/endocr/bqaf065","DOIUrl":"10.1210/endocr/bqaf065","url":null,"abstract":"Infertility represents a major global health challenge, with male infertility accounting for a significant proportion of cases, yet its underlying causes remain elusive in many instances. Traditionally, spermatozoa were viewed merely as DNA carriers, with little consideration given to their role beyond fertilization. Recent research, however, is challenging this view, revealing that spermatozoa are far more than passive delivery vehicles. They carry a complex array of molecules, particularly RNAs, which actively influence fertilization, early embryo development, and the transmission of paternal traits. These sperm-carried RNAs, including mRNAs, small RNAs, and noncoding RNAs, regulate gene expression in both spermatozoa and embryo, with profound implications for offspring development. Additionally, environmental factors, such as lifestyle choices and exposure to toxins, have been shown to affect sperm RNA composition, highlighting the dynamic interplay between genetics and the environment in shaping fertility. This emerging and evolving understanding of sperm function challenges traditional reproductive biology and offers new insights into male infertility, particularly in cases that remain unexplained by current diagnostic methods. Although the exact molecular mechanisms underlying these processes are still being investigated, this paradigm shift opens the door to innovative diagnostic tools and therapeutic strategies for treating male infertility. By uncovering the critical role of sperm RNAs, these findings not only enhance our understanding of reproductive biology but also hold the promise to improve assisted reproductive technologies and outcomes for infertile couples.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143779393","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

Manganese-induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation in Female Rats. 锰诱导的性早熟改变雌性大鼠乳腺上皮细胞增殖。

IF 3.8 3区医学

Endocrinology Pub Date : 2025-03-24 DOI: 10.1210/endocr/bqaf052

Alina M Hamilton, Vinod K Srivastava, Jill K Hiney, William L Dees, Robert K Dearth

{"title":"Manganese-induced Precocious Puberty Alters Mammary Epithelial Cell Proliferation in Female Rats.","authors":"Alina M Hamilton, Vinod K Srivastava, Jill K Hiney, William L Dees, Robert K Dearth","doi":"10.1210/endocr/bqaf052","DOIUrl":"10.1210/endocr/bqaf052","url":null,"abstract":"Precocious puberty (PP) is an established breast cancer risk factor. In the normal mammary gland, hormone receptor-positive (HR+) cells rarely proliferate. In breast cancer, proliferating epithelial cells are often HR+. It is not known if PP can modify this population of proliferating HR+ cells. Previously, we established a manganese-induced precocious puberty (MnPP) model to study the effects of PP on mammary gland development in female rats. Here, we characterized the distribution of HR+ proliferating mammary epithelial cells in prepubertal and adult rodents, in association with precocious puberty. Female rats were exposed daily to 10 mg/kg manganese chloride or saline (control) from postnatal day (PND) 12 to PND 30. Mammary glands were collected on PNDs 30 and 120, processed for western blot analysis and double immunofluorescence staining for proliferating cell nuclear antigen and progesterone receptor or estrogen receptor. MnPP increased the percentage of HR+ mammary epithelial cells coexpressing proliferating cell nuclear antigen relative to normally developed controls at PND 30. This correlated with increased expression of estrogen receptor-regulated proteins in MnPP mammary glands relative to controls at PND 30, including FOXA1, AREG, and c-Myc. Conversely, at PND 120 relative to PND 30, proliferating HR+ cells remained chronically elevated in MnPP mammary glands at PND 120, which coincided with decreased expression of cell-cycle regulator, p27, and increased expression of progesterone receptor-regulated markers, EREG and sp1. Collectively, these results suggest early puberty alters steroidal regulation of classic proliferative mechanisms in the prepubertal gland with increased prevalence of high-risk proliferating HR+ cells.","PeriodicalId":11819,"journal":{"name":"Endocrinology","volume":" ","pages":""},"PeriodicalIF":3.8,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006721/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143656544","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