Rachael P Norris, Laurinda A Jaffe
Signaling in the granulosa cells of mammalian ovarian follicles is necessary for maintaining prophase arrest in the oocyte and for mediating the resumption of meiosis in response to luteinizing hormone (LH). However, the follicle also includes an outer layer of theca cells, some of which express receptors for LH. To investigate whether the theca cells are required for maintaining meiotic arrest and reinitiating meiosis in response to LH, we mechanically separated the granulosa cells and oocyte from the theca and basal lamina...
January 5, 2024: Endocrinology
Aleisha M Moore, Alyssa G Novak, Michael N Lehman
There is considerable evidence that synchronized activity within a reciprocally connected population of cells in the arcuate nucleus (ARC) co-expressing kisspeptin, neurokinin B (NKB) and dynorphin (KNDy cells) is crucial for the generation of gonadotrophin-releasing hormone (GnRH) pulses in mammals. The initial "KNDy hypothesis" proposed that pulsatile GnRH secretion is elicited by episodic kisspeptin release from KNDy cells following synchronized activation and termination of the population by NKB and dynorphin, respectively...
January 3, 2024: Endocrinology
Vaibhave Ubba, Serene Joseph, Olubusayo Awe, Dustin Jones, Milan K Dsilva, Mingxiao Feng, Junjiang Wang, Xiaomin Fu, Razeen J Akbar, Brittany H Bodnar, Wenhui Hu, Hong Wang, Xiaofeng Yang, Ling Yang, Peixin Yang, Bouchra Taib, Rexford Ahima, Sara Divall, Sheng Wu
Hyperandrogenism and polycystic ovarian syndrome (PCOS) result from the imbalance or increase of androgen levels in females. Androgen Receptor (AR) mediates the effects of androgens, and this study examines whether neuronal AR plays a role in reproduction under normal and increased androgen conditions in female mice. The neuron specific AR knockout mouse (SynARKO) was generated from a female mouse (synapsin promoter driven Cre) and a male mouse (Ar fl/y). Puberty onset and the levels of reproductive hormones such as LH, FSH, testosterone and estradiol were comparable between the control and the SynARKO mice...
December 29, 2023: Endocrinology
Lauryn Choleva, Peng Wang, Hongtao Liu, Olivia Wood, Luca Lambertini, Donald K Scott, Esra Karakose, Andrew F Stewart
Mutations in CDKN1C, encoding p57KIP2, a canonical cell cycle inhibitor, underlie multiple pediatric endocrine syndromes. Despite this central role in disease, little is known about the structure and function of p57KIP2 in the human pancreatic beta cell. Since p57KIP2 is predominantly nuclear in human beta cells, we hypothesized that disease-causing mutations in its nuclear localization sequence (NLS) may correlate with abnormal phenotypes. We prepared RIP1 insulin promoter-driven adenoviruses encoding deletions of multiple disease-associated but unexplored regions of p57KIP2, and performed a comprehensive structure-function analysis of CDKN1C/p57KIP2...
December 28, 2023: Endocrinology
Rebecca E Ruggiero-Ruff, Brandon H Le, Pedro A Villa, Nancy M Lainez, Sandria W Athul, Pratyusa Das, Buffy S Ellsworth, Djurdjica Coss
Obesity is a chronic disease with increasing prevalence worldwide. Obesity leads to an increased risk of heart disease, stroke, and diabetes; as well as endocrine alterations, reproductive disorders, changes in basal metabolism, and stress hormone production, all of which are regulated by the pituitary. In this study, we performed single cell RNA sequencing (scRNA-seq) of pituitary glands from male mice fed control (CTR) and high-fat diet (HFD), to determine obesity-mediated changes in pituitary cell populations and gene expression...
December 26, 2023: Endocrinology
Ya-Nan Zhu, Fan Pan, Xiao-Wen Gan, Yun Liu, Wang-Sheng Wang, Kang Sun
Progesterone synthesized in the placenta is essential for pregnancy maintenance. CYP11A1 is a key enzyme in progesterone synthesis, and its expression increases greatly during trophoblast syncytialization. However, the underlying mechanism remains elusive. Here, we demonstrated that passive demethylation of CYP11A1 promoter accounted for the upregulation of CYP11A1 expression during syncytialization with the participation of the transcription factor C/EBPα. We found that the methylation rate of a CpG locus in CYP11A1 promoter was significantly reduced along with decreased DNA methyltransferase 1 (DNMT1) expression and its enrichment at CYP11A1 promoter during syncytialization...
December 26, 2023: Endocrinology
Jillian Wilbourne, Shuai Jia, Allyssa Fogarty, Motoki Takaku, Fei Zhao
Wolffian duct (WD) maintenance and differentiation is predominantly driven by the androgen action, which is mediated by the androgen receptor (AR). It is well established that the mesenchyme indicates the fate and differentiation of epithelial cells. However, in vivo developmental requirement of mesenchymal AR in Wolffian duct development is still undefined. By designing a mesenchyme-specific Ar knockout (ARcKO), we discovered that the loss of mesenchymal Ar led to the bilateral or unilateral degeneration of caudal Wolffian ducts and cystic formation at the cranial Wolffian ducts...
December 26, 2023: Endocrinology
Abraham Behrmann, Dalian Zhong, Li Li, Shangkui Xie, Megan Mead, Parastoo Sabaeifard, Mohammad Goodarzi, Andrew Lemoff, Julia Kozlitina, Dwight A Towler
Wnt16 is expressed in bone and arteries, and maintains bone mass in mice and humans, but its role in cardiovascular physiology is unknown. We show that Wnt16 protein accumulates in murine and human vascular smooth muscle (VSM). WNT16 genotypes that convey risk for bone frailty also convey risk for cardiovascular events in Dallas Heart Study. Murine Wnt16 deficiency, which causes postnatal bone loss, also reduced systolic blood pressure. Electron microscopy demonstrated abnormal VSM mitochondrial morphology in Wnt16-null mice, with reductions in mitochondrial respiration...
December 20, 2023: Endocrinology
Sudhaker D Rao, Bhanu Malhotra, Sanjay Kumar Bhadada
No abstract text is available yet for this article.
December 16, 2023: Endocrinology
Tiffany K Miles, Angela K Odle, Stephanie D Byrum, Alex Lagasse, Anessa Haney, Victoria G Ortega, Cole R Bolen, Jewel Banik, Milla M Reddick, Ashley Herdman, Melanie C MacNicol, Angus M MacNicol, Gwen V Childs
Anterior pituitary cell function requires a high level of protein synthesis and secretion which depend heavily on mitochondrial ATP production and functional endoplasmic reticula. Obesity adds stress to tissues, requiring them to adapt to inflammation and oxidative stress, and adding to their allostatic load. We hypothesized that pituitary function is vulnerable to the stress of obesity. Here, we utilized a 10-15 week high fat diet (HFD, 60%) in a thermoneutral environment to promote obesity, testing both male and female FVB...
December 16, 2023: Endocrinology
Elvira Crescenzi, Stefano Mellone, Gianluca Gragnano, Antonino Iaccarino, Antonio Leonardi, Francesco Pacifico
Neutrophil Gelatinase-Associated Lipocalin (NGAL), a siderophore-mediated iron binding protein, is highly expressed in human anaplastic thyroid carcinomas (ATC) where it plays pleiotropic pro-tumorigenic roles including that of pro-survival protein. Here we show that NGAL inhibits FAS/CD95 death receptor to control ATC cells survival. FAS/CD95 expression in human specimens from ATC patients and in ATC-derived cell lines negatively correlate with NGAL expression. Silencing of NGAL in ATC cells leads to FAS/CD95 up-regulation, whereas NGAL over-expression determines the opposite effect...
December 13, 2023: Endocrinology
Jones B Graceli, Helena D Zomer, Theresa I Medrano, Rex A Hess, Kenneth S Korach, Paul S Cooke
Estrogen actions are mediated by both nuclear (n) and membrane (m) localized estrogen receptor 1 (ESR1). Male Esr1 knockout (Esr1KO) mice lacking functional Esr1 are infertile, with reproductive tract abnormalities. Male mice expressing nESR1 but lacking mESR1 (nuclear-only estrogen receptor 1 [NOER] mice) are progressively infertile due to testicular, rete testis and efferent ductule abnormalities similar to Esr1KO males, indicating a role for mESR1 in male reproduction. The H2NES mouse expresses only mESR1 but lacks nESR1...
December 8, 2023: Endocrinology
Rupak Thapa, Logan Druessel, Liang Ma, Donald S Torry, Brent M Bany
During the secretory phase of the menstrual cycle, elongated fibroblast-like mesenchymal cells in the uterine endometrium begin to trans-differentiate into polygonal epithelioid-like (decidual) cells. This decidualization process continues more broadly during early pregnancy, and the resulting decidual tissue supports successful embryo implantation and placental development. This study was carried out to determine if atonal basic helix-loop-helix transcription factor 8 (ATOH8) plays a role in human endometrial stromal fibroblast (ESF) decidualization...
December 7, 2023: Endocrinology
Nadia Saadat, Joseph Ciarelli, Brooke Pallas, Vasantha Padmanabhan, Arpita Kalla Vyas
Gestational hyperandrogenism adversely impacts offspring health. Using an ovine model, we found prenatal testosterone (T) excess adversely affects growth and cardiometabolic outcomes in female offspring and sex-specific effects on fetal myocardium. Since lipids are essential to cardiometabolic function, we hypothesized that prenatal T excess will lead to sex-specific disruptions in lipid metabolism at birth. Shotgun lipidomics was performed on the plasma samples collected 48 hours after birth from female (F) and male (M) lambs of control (C) and (T) sheep (CF=4, TF=7, CM=5, TM=10) and data analyzed by univariate analysis, multivariate dimensionality reduction modeling followed by functional enrichment and pathway analyses...
December 7, 2023: Endocrinology
Juan Pablo Robles, Magdalena Zamora, Jose F Garcia-Rodrigo, Alma Lorena Perez, Thomas Bertsch, Gonzalo Martinez de la Escalera, Jakob Triebel, Carmen Clapp
Vasoinhibin is a proteolytic fragment of the hormone prolactin that inhibits blood vessel growth (angiogenesis) and permeability, stimulates the apoptosis and inflammation of endothelial cells and promotes fibrinolysis. The antiangiogenic and antivasopermeability properties of vasoinhibin were recently traced to the HGR motif located in residues 46 to 48, allowing the development of potent, orally active, HGR-containing vasoinhibin analogs for therapeutic use against angiogenesis-dependent diseases. However, whether the HGR motif is also responsible for the apoptotic, inflammatory, and fibrinolytic properties of vasoinhibin has not been addressed...
December 6, 2023: Endocrinology
Tianzhichao Hou, Qi Wang, Huajie Dai, Yanan Hou, Jie Zheng, Tiange Wang, Hong Lin, Shuangyuan Wang, Mian Li, Zhiyun Zhao, Yuhong Chen, Yu Xu, Jieli Lu, Ruixin Liu, Guang Ning, Weiqing Wang, Min Xu, Yufang Bi
CONTEXT: The association between the gut microbiota and thyroid cancer remains controversial. OBJECTIVE: We aimed to systematically investigate the interactive causal relationships between the abundance and metabolism pathways of gut microbiota and thyroid cancer. METHODS: We leveraged genome-wide association studies for the abundance of 211 microbiota taxa from the MiBioGen study (N = 18,340), 205 microbiota metabolism pathways from the Dutch Microbiome Project (N = 7738), and thyroid cancer from the Global Biobank Meta-analysis Initiative (N cases = 6699 and N participants = 1,620,354)...
December 5, 2023: Endocrinology
Katherine Kim, Mita Varghese, Haijing Sun, Simin Abrishami, Emily Bowers, Dave Bridges, Jennifer L Meijer, Kanakadurga Singer, Brigid Gregg
Obesity and metabolic diseases are rising in women of reproductive age, increasing offspring metabolic risk. Maternal nutritional interventions during lactation present an opportunity to modify offspring outcomes. We previously demonstrated in mice that adult male offspring have metabolic impairments and increased adipose tissue macrophages (ATM) when dams are fed high fat diet (HFD) during the postnatal lactation window (HFD PN). We sought to understand the effect of HFD during lactation on early life inflammation...
December 4, 2023: Endocrinology
Hye-Eun Byeon, Sung-E Choi, Yujin Kim, Suji Choi, Soo-Jin Lee, Dong Hyun Kim, Jung-Soon Mo, Ja Young Jeon
Histone deacetylase 11 (HDAC11) has been implicated in the pathogenesis of metabolic diseases characterized by chronic low-grade inflammation, such as obesity. However, the influence of HDAC11 on inflammation and the specific effect of HDAC11 on the palmitic acid (PA)-induced NLR family pyrin domain containing 3 (NLRP3) inflammasome activation are poorly understood. The effect of PA treatment on HDAC11 activity and the NLRP3 inflammasome was investigated in human peripheral blood mononuclear cells and THP-1 cells...
January 16, 2024: Endocrinology
Jani Liimatta, Evelyn Curschellas, Emre Murat Altinkilic, Rawda Naamneh Elzenaty, Philipp Augsburger, Therina du Toit, Clarissa D Voegel, David T Breault, Christa E Flück, Emanuele Pignatti
Cholesterol is the precursor of all steroids, but how cholesterol flux is controlled in steroidogenic tissues is poorly understood. The cholesterol exporter ABCG1 is an essential component of the reverse cholesterol pathway and its global inactivation results in neutral lipid redistribution to tissue macrophages. The function of ABCG1 in steroidogenic tissues, however, has not been explored. To model this, we inactivated Abcg1 in the mouse adrenal cortex, which led to an adrenal-specific increase in transcripts involved in cholesterol uptake and de novo synthesis...
January 16, 2024: Endocrinology
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