Molecular and Cellular Endocrinology最新文献

Hyperthyroidism is becoming increasingly important as an independent risk factor for cardiovascular disease, eventually resulting in cardiac hypertrophy and heart failure. The 14-3-3 protein family subtypes regulate many cellular processes in eukaryotes by interacting with a diverse array of client proteins. Considering that the 14-3-3η protein protects cardiomyocytes by affecting mitochondrial function, exploring the biological influence and molecular mechanisms by which 14-3-3η alleviates the cardiac hypertrophy of hyperthyroidism is imperative. In vivo and in vitro, RT-PCR, Western blot, and Mitochondrial tracking assay were performed to understand the molecular mechanism of thyroxine-induced cardiomyocyte hypertrophy. HE staining, transmission electron microscopy, and immunofluorescence were used to observe intuitively changes of hearts and cardiomyocytes. The in vivo and in vitro results indicated that overexpression of the 14-3-3η ameliorated thyroxine-induced cardiomyocyte hypertrophy, whereas knockdown of the 14-3-3η protein aggravated thyroxine-induced cardiomyocyte hypertrophy. Additionally, overexpression of the 14-3-3η protein reduces thyroxine-induced mitochondrial damage and mitophagy in cardiomyocytes. Overexpression of 14-3-3η protein improves excessive mitophagy in the myocardium caused by thyroxine and thus prevents cardiac hypertrophy.

Previous studies have indicated a complex interplay between the nitric oxide (NO) pain signaling pathways and hormonal signaling pathways in the body. This article delineates the role of nitric oxide signaling in neuropathic and inflammatory pain generation and subsequently discusses how the neuroendocrine system is involved in pain generation. Hormonal systems including the hypothalamic-pituitary axis (HPA) generation of cortisol, the renin-angiotensin-aldosterone system, calcitonin, melatonin, and sex hormones could potentially contribute to the generation of nitric oxide involved in the sensation of pain. Further research is necessary to clarify this relationship and may reveal therapeutic targets involving NO signaling that alleviate neuropathic and inflammatory pain.

Menopause causes important bodily and metabolic changes, which favor the increased occurrence of cardiovascular diseases, obesity, diabetes, and osteoporosis. Resveratrol exerts proven effects on body metabolism, improving glucose and lipid homeostasis and reducing inflammation and oxidative stress in various organs and tissues. Accordingly, this study evaluates the effects of resveratrol supplementation on the expression of markers associated with thermogenesis in brown adipose tissue, and on the body, metabolic and hormonal parameters of female mice submitted to bilateral oophorectomy. Eighteen female mice were randomized into three groups: G1: control (CONTROL), G2: oophorectomy (OOF), and G3: oophorectomy + resveratrol (OOF + RSV); the animals were kept under treatment for twelve weeks, being fed a standard diet and treated with resveratrol via gavage. Body, biochemical, hormonal, and histological parameters were measured; in addition to the expression of markers associated with thermogenesis in brown adipose tissue. The results showed that animals supplemented with resveratrol showed reduced body weight and visceral adiposity, in addition to glucose, total cholesterol, and triglyceride levels; decreased serum FSH levels and increased estrogen levels were observed compared to the OOF group and mRNA expression of PRDM16, UCP1, and SIRT3 in brown adipose tissue. The findings of this study suggest the important role of resveratrol in terms of improving body, metabolic, and hormonal parameters, as well as modulating markers associated with thermogenesis in brown adipose tissue of female mice submitted to oophorectomy.

Mammary gland (MG) lactogenic differentiation involves epigenetic mechanisms. We have previously shown that hypothyroidism (HypoT) alters the MG transcriptome in lactation. However, the role of thyroid hormones (T3 and T4 a. k.a. THs) in epigenetic differentiation of MG is still unknown. We used a model of post-lactating HypoT rats to study in MG: a) Methylation and expression level of Gata3, Elf5, Stat6, Stat5a, Stat5b; b) Expression of Lalba, IL-4Rα and Ncoa1 mRNA; c) Histone H3 acetylation and d) Estrogen and progesterone concentration in serum. HypoT increases the estrogen serum level, decreases the progesterone level, promotes methylation of Stat5a, Stat5b and Stat6, decreasing their mRNA level and of its target genes (Lalba and IL-4Rα) and increases the Ncoa1 mRNA expression and histone H3 acetylation level. Our results proved that HypoT alters the post-lactation MG epigenome and could compromise mammary functional differentiation.

This paper provides a summary of the role of nitric oxide (NO) and hormones in the development of chronic stress, anxiety, depression, and post-traumatic stress disorder (PTSD). These mental health conditions are prevalent globally and involve complex molecular interactions. Although there is a significant amount of research and therapeutic options available, the underlying mechanisms of these disorders are still not fully understood. The primary pathophysiologic processes involved in chronic stress, anxiety, depression, and PTSD include dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis, the intracellular influence of neuronal nitric oxide synthase (nNOS) on transcription factors, an inflammatory response with the formation of nitrergic oxidative species, and reduced serotonergic transmission in the dorsal raphe nucleus. Despite the extensive literature on this topic, there is a great need for further research to clarify the complexities inherent in these pathways, with the primary aim of improving psychiatric care.

Reproductive factors play significantly important roles in determining the breast cancer (BC) risk. The impact of pregnancy, abortion, and birth control methods on tumor development remains unclear. It has been found that early full-term pregnancies in young women can lower their lifetime risk of developing the type of cancer in question. However, having a first full-term pregnancy at an older age can increase this risk. The relationship between pregnancy and breast cancer (BC) is, however, much more complicated. Both induced and spontaneous abortions lead to sudden changes in hormonal balance, which could cause different effects on sensitive breast epithelial cells, making abortion a potential risk factor for breast cancer. The influence of hormonal contraception on carcinogenesis is not comprehensively understood, and therefore, more exhaustive analysis of existing data and further investigation is needed. This review explores how the mentioned reproductive factors affect the risk of breast cancer (BC), focusing on the molecular mechanisms that contribute to its complexity. By comprehending this intricate network of relationships, we can develop new strategies for predicting and treating the disease.

The neuroendocrine system of crustaceans is complex and regulates many processes, such as development, growth, reproduction, osmoregulation, behavior, and metabolism. Once stimulated, crustaceans’ neuroendocrine tissues modulate the release of monoamines, ecdysteroids, and neuropeptides that can act as hormones or neurotransmitters. Over a few decades, research has unraveled some mechanisms governing these processes, substantially contributing to understanding crustacean physiology. More aspects of crustacean neuroendocrinology are being comprehended with molecular biology, transcriptome, and genomics analyses. Hence, these studies will also significantly enhance the ability to cultivate decapods, such as crabs and shrimps, used as human food sources. In this review, current knowledge on crustacean endocrinology is updated with new findings about crustacean hormones, focusing mainly on the main neuroendocrine organs and their hormones and the effects of these molecules regulating metabolism, growth, reproduction, and color adaptation. New evidence about vertebrate-type hormones found in crustaceans is included and discussed. Finally, this review may assist in understanding how the emerging chemicals of environmental concern can potentially impair and disrupt crustacean's endocrine functions and their physiology.

Hyperglycemia is a key contributor to diabetic macrovascular and ocular complications. It triggers a cascade of cellular damage, particularly in the retinal microvascular endothelial cells (RMECs). However, the underlying molecular mechanisms remain only partially understood. This study hypothesizes that CircZNF609 plays a pivotal role in mediating high glucose-induced damage in RMECs by modulating miR-150-5p and its downstream target genes, thereby affecting cellular survival, apoptosis, and oxidative stress. Gene expression datasets (GSE193974 and GSE160308) and clinical samples were used to investigate the expression levels of CircZNF609 and its interaction with miR-150-5p in the context of diabetic retinopathy (DR). Our results demonstrate that CircZNF609 is upregulated in both peripheral blood stem cells from DR patients and high glucose-stimulated hRMECs. Functional experiments reveal that silencing CircZNF609 improves cell viability, reduces apoptosis, inhibits tube formation, and modulates oxidative stress markers, whereas CircZNF609 overexpression exacerbates these effects. Moreover, miR-150-5p, a microRNA, was found to be negatively regulated by CircZNF609 and downregulated in DR. Its overexpression mitigates high glucose-induced cell injury. Our findings suggest a novel mechanism whereby CircZNF609 exacerbates high glucose-induced endothelial cell damage by sponging miR-150-5p, implicating the CircZNF609/miR-150-5p axis as a potential therapeutic target in diabetic retinopathy.

During insulin resistance, the heart undergoes a metabolic shift in which fatty acids (FA) account for roughly about 99% of the ATP production. This metabolic shift is indicative of impaired glucose metabolism. A shift in FA metabolism with impaired glucose tolerance can increase reactive oxygen species (ROS), lipotoxicity, and mitochondrial dysfunction, ultimately leading to cardiomyopathy. Thyroid hormones (TH) may improve the glucose intolerance by increasing glucose reabsorption and metabolism in peripheral tissues, but little is known on its effects on cardiac tissue during insulin resistance. In the present study, insulin resistant Otsuka Long Evans Tokushima Fatty (OLETF) rats were used to assess the effects of exogenous thyroxine (T4) on glucose metabolism in cardiac tissue. Rats were assigned to four groups: (1) lean, Long Evans Tokushima Otsuka (LETO; n=6), (2) LETO + T4 (8 μg/100 g BM/d × 5 wks; n = 7), (3) untreated OLETF (n = 6), and (4) OLETF + T4 (8 μg/100 g BM/d × 5 wks; n = 7). T4 increased GLUT4 gene expression by 85% in OLETF and increased GLUT4 protein translocation to the membrane by 294%. Additionally, T4 increased p-AS160 by 285%, phosphofructokinase-1 (PFK-1) mRNA, the rate limiting step in glycolysis, by 98% and hexokinase II by 64% in OLETF. T4 decreased both CPT2 mRNA and protein expression in OLETF. The results suggest that exogenous T4 has the potential to increase glucose uptake and metabolism while simultaneously reducing fatty acid transport in the heart of insulin resistant rats. Thus, L-thyroxine may have therapeutic value to help correct the impaired substrate metabolism associated with diabetic cardiomyopathy.

Young women undergoing anticancer treatment are at risk of premature ovarian failure (POF). Endometrial-derived stem cells (EnSCs) have demonstrated significant therapeutic potential for treating ovarian insufficiency, although the underlying mechanisms remain to be fully understood. This study aims to further investigate the therapeutic effects of EnSCs, particularly through the paracrine action of fibroblast growth factor 2 (FGF2), on POF. The findings show that exogenous FGF2 enhances the survival of ovarian granulosa cells damaged by cisplatin. FGF2 stimulates the proliferation of these damaged cells by suppressing the Hippo signaling pathway and activating YAP expression. In vivo experiments also revealed that FGF2 treatment significantly improves ovarian reserve and endocrine function in mice with POF. These results suggest that FGF2 can boost the proliferative capacity of damaged ovarian granulosa cells through the Hippo-YAP signaling pathway, providing a theoretical foundation for using EnSCs and FGF2 in clinical treatments for POF.