Endocrinology

https://academic.oup.com/endo

List of Papers (Total 10,514)

Chronic Exposure of Mice to Bisphenol-A Alters Uterine Fibroblast Growth Factor Signaling and Leads to Aberrant Epithelial Proliferation

Uterine epithelial proliferation is regulated in a paracrine manner by a complex interplay between estrogen (E) and progesterone (P) signaling, in which E stimulates proliferation and P inhibits it. Perturbation of steroid hormone signaling within the uterine milieu could contribute to the development of endometrial hyperplasia and cancer. It is well established that bisphenol-A...

Prolactin Receptor Signaling Regulates a Pregnancy-Specific Transcriptional Program in Mouse Islets

Pancreatic β-cells undergo profound hyperplasia during pregnancy to maintain maternal euglycemia. Failure to reprogram β-cells into a more replicative state has been found to underlie susceptibility to gestational diabetes mellitus (GDM). We recently identified a requirement for prolactin receptor (PRLR) signaling in the metabolic adaptations to pregnancy, where β-cell–specific...

The Activin Social Network: Activin, Inhibin, and Follistatin in Breast Development and Cancer

Activins and inhibins are closely related protein heterodimers with a similar tissue distribution; however, these two complexes have opposing functions in development and disease. Both are secreted cytokine hormones, with activin the primary inducer of downstream signaling cascades and inhibin acting as a rheostat that exquisitely governs activin function. Adding to the...

Metabolic Abnormalities of Chronic High-Dose Glucocorticoids Are Not Mediated by Hypothalamic AgRP in Male Mice

Glucocorticoids are potent and widely used medicines but often cause metabolic side effects. A murine model of corticosterone treatment resulted in increased hypothalamic expression of the melanocortin antagonist AgRP in parallel with obesity and hyperglycemia. We investigated how these adverse effects develop over time, with particular emphasis on hypothalamic involvement. Wild...

Intestine-Specific Overexpression of LDLR Enhances Cholesterol Excretion and Induces Metabolic Changes in Male Mice

Roux-en-Y gastric bypass (RYGB) surgery is one of the most effective treatment options for severe obesity and related comorbidities, including hyperlipidemia, a well-established risk factor of cardiovascular diseases. Elucidating the molecular mechanisms underlying the beneficial effects of RYGB may facilitate development of equally effective, but less invasive, treatments...

Quantitative Proteomics by SWATH-MS of Maternal Plasma Exosomes Determine Pathways Associated With Term and Preterm Birth

Exosomes are membrane-bound nanovesicles that transport molecular signals between cells. This study determined changes in maternal plasma exosome proteomics contents in term and preterm births. Maternal plasma (MP) samples were collected from group 1: term not in labor (TNIL, n = 13); group 2: term in labor (TL, n = 11); group 3: preterm premature rupture of membranes (pPROM, n...

Kisspeptin Stimulation of Prolactin Secretion Requires Kiss1 Receptor but Not in Tuberoinfundibular Dopaminergic Neurons

Kisspeptin has been shown to stimulate prolactin secretion. We investigated whether kisspeptin acts through the Kiss1 receptor (Kiss1r) to regulate dopamine and prolactin. Initially, we evaluated prolactin response in a Kiss1r-deficient mouse line, in which Kiss1r had been knocked into GnRH neurons (Kiss1r−/−R). Intracerebroventricular kisspeptin-10 (Kp-10) increased prolactin...

Epithelial Mutations in Endometriosis: Link to Ovarian Cancer

Epidemiologic and histopathologic associations between endometriosis and epithelial ovarian cancer have been reported; however, the underlying molecular and cellular mechanisms are not well understood. A possible genetic link has been suggested in recent publications. Driver mutations in PIK3CA, KRAS, ARID1A, and other genes have been found in the epithelium of intrauterine...

Prenatal Bisphenol A Exposure in Mice Induces Multitissue Multiomics Disruptions Linking to Cardiometabolic Disorders

The health impacts of endocrine-disrupting chemicals (EDCs) remain debated, and their tissue and molecular targets are poorly understood. In this study, we leveraged systems biology approaches to assess the target tissues, molecular pathways, and gene regulatory networks associated with prenatal exposure to the model EDC bisphenol A (BPA). Prenatal BPA exposure at 5 mg/kg/d, a...

Circulating Exosomal miRNA Profile During Term and Preterm Birth Pregnancies: A Longitudinal Study

Despite decades of research in the field of human reproduction, the mechanisms responsible for human parturition still remain elusive. The objective of this study was to describe the changes in the exosomal miRNA concentrations circulating in the maternal plasma between mothers delivering term and preterm neonates, across gestation using a longitudinal study design. This...

Shedding Perspective on Extracellular Vesicle Biology in Diabetes and Associated Metabolic Syndromes

The etiology of diabetes and associated metabolic derailments is a complex process that relies on crosstalk between metabolically active tissues. Dysregulation of secreted factors and metabolites from islets, adipose tissue, liver, and skeletal muscle contributes to the overall progression of diabetes and metabolic syndrome. Extracellular vesicles (EVs) are circulating...

Sex-Dimorphic and Sex Hormone–Dependent Role of Steroid Sulfatase in Adipose Inflammation and Energy Homeostasis

Steroid sulfatase (STS), a desulfating enzyme that converts steroid sulfates to hormonally active steroids, plays an important role in the homeostasis of sex hormones. STS is expressed in the adipose tissue of both male and female mice, but the role of STS in the development and function of adipose tissue remains largely unknown. In this report, we show that the adipose...

Olfactomedin 4 Deletion Improves Male Mouse Glucose Intolerance and Insulin Resistance Induced by a High-Fat Diet

Glucose-stimulated insulin secretion (GSIS) is essential for blood glucose homeostasis and is impaired in type 2 diabetes mellitus. Understanding the regulatory components of GSIS has clinical implications for diabetes treatment. In this study, we found that olfactomedin 4 (OLFM4) is endogenously expressed in pancreatic islet β cells and further investigated its potential roles...

Endothelial Insulin Receptor Restoration Rescues Vascular Function in Male Insulin Receptor Haploinsufficient Mice

Reduced systemic insulin signaling promotes endothelial dysfunction and diminished endogenous vascular repair. We investigated whether restoration of endothelial insulin receptor expression could rescue this phenotype. Insulin receptor knockout (IRKO) mice were crossed with mice expressing a human insulin receptor endothelial cell–specific overexpression (hIRECO) to produce IRKO...

Retinoid X Receptor Activation During Adipogenesis of Female Mesenchymal Stem Cells Programs a Dysfunctional Adipocyte

Early life exposure to endocrine-disrupting chemicals (EDCs) is an emerging risk factor for the development of obesity and diabetes later in life. We previously showed that prenatal exposure to the EDC tributyltin (TBT) results in increased adiposity in the offspring. These effects linger into adulthood and are propagated through successive generations. TBT activates two nuclear...

Nicotinamide Nucleotide Transhydrogenase as a Novel Treatment Target in Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is an aggressive malignancy with poor response to chemotherapy. In this study, we evaluated a potential new treatment target for ACC, focusing on the mitochondrial reduced form of NAD phosphate (NADPH) generator nicotinamide nucleotide transhydrogenase (NNT). NNT has a central role within mitochondrial antioxidant pathways, protecting cells from...

Elucidating the Role of the Maternal Embryonic Leucine Zipper Kinase in Adrenocortical Carcinoma

Adrenocortical carcinoma (ACC) is an aggressive cancer with a 5-year survival rate <35%. Mortality remains high due to lack of targeted therapies. Using bioinformatic analyses, we identified maternal embryonic leucine zipper kinase (MELK) as 4.1-fold overexpressed in ACC compared with normal adrenal samples. High MELK expression in human tumors correlated with shorter survival...

Profiling of 3696 Nuclear Receptor–Coregulator Interactions: A Resource for Biological and Clinical Discovery

Nuclear receptors (NRs) are ligand-inducible transcription factors that play critical roles in metazoan development, reproduction, and physiology and therefore are implicated in a broad range of pathologies. The transcriptional activity of NRs critically depends on their interaction(s) with transcriptional coregulator proteins, including coactivators and corepressors. Short...

EF24 (a Curcumin Analog) and ZSTK474 Emphasize the Effect of Cabozantinib in Medullary Thyroid Cancer

XL184 is a small-molecule kinase inhibitor recently included in first-line systemic therapy for patients with advanced, progressive medullary thyroid cancer (MTC). EF24 is a curcumin analog with a high bioavailability, and ZSTK474 is an inhibitor of the phosphatidylinositol 3-kinase signaling pathway. We investigated the effect of these compounds, alone and in combination, in two...