Molecular and Cellular Endocrinology最新文献

The study aimed to investigate the repercussions of androgen modulation on the adrenal cortex of male gerbils, focusing on the morphophysiology, proliferation, and cell death, as well as the expression of hormone receptors and steroidogenic enzymes. Mongolian gerbils (Meriones unguiculatus) were divided into three experimental groups: Control (C), Testosterone (T), animals received injections of testosterone cypionate and Castrated (Ct), animals underwent orchiectomy. The results showed that castration increased the zona fasciculata and promoted cell hypertrophy in all zones. Testosterone supplementation increased cell proliferation and cell death. Androgen modulation promoted an increase in AR, Erα, and ERβ. Castration promoted an increase in the CYP19, while decreasing 17βHSD enzymes. Testosterone supplementation, on the other hand, reduced CYP17 and increased CYP19 and 3βHSD enzymes. By analyzing the effects of androgen supplementation and deprivation, it can be concluded that testosterone is responsible for tissue remodeling in the cortex, regulating the rate of cell proliferation and death, as well as cell hypertrophy. Testosterone also modulate steroid hormone receptors and steroidogenic enzymes, consequently affecting the regulation, hormone synthesis and homeostasis of this endocrine gland.

Low temperatures significantly influence feeding behavior in ectothermic vertebrates, but the underlying mechanisms remain elusive. This study investigated the role of transient receptor potential ankyrin 1 (TRPA1) channels in mediating the appetite-suppressing effects of low temperature in Nile tilapia. TRPA1 was found to be highly expressed in the hypothalamus and co-localized with neuropeptide Y (NPY) neurons. Exposure to low temperatures reduced feeding frequency and increased TRPA1 expression. In vitro experiments demonstrated that low temperature and TRPA1 agonists induced calcium influx, which was blocked by a TRPA1 inhibitor. TRPA1 expression exhibited post-prandial increases and was downregulated by fasting. TRPA1 activation dose-dependently inhibited food intake, while its inhibition restored feeding suppressed by low temperature. TRPA1 activation downregulated orexigenic factors and upregulated anorexigenic factors through Ca²⁺/calmodulin-dependent pathways. These findings suggest that TRPA1 plays a crucial role in sensing low temperatures and regulating feeding behavior in tilapia.

Graves' disease (GD), an autoimmune thyroid disease, is one of the main autoimmune diseases in the general population. It is known that the pathophysiology of this disease may be related to immunological mechanisms dysregulation. These mechanisms can be influenced by GD therapies, such as iodide or antithyroid drugs (ATD).

Objective

Verify relation between clinical, biochemical and treatment modalities used prior to surgery and histopathological characteristics observed in total thyroidectomy products from patients previously diagnosed with Graves' disease. Furthermore, these data were related to composition of lymphocytic infiltrate in terms of proportions of lymphocytes CD4⁺, CD8⁺, CD25⁺ and CD20⁺. We aim to contribute to the understanding of the evolution pattern of GD, whose pathophysiology is not yet completely understood.

Methods

Cross-sectional study assessing thyroidectomy products for the presence of lymphocytic infiltrate, as well as the proportion and intensity of CD4⁺, CD8⁺, CD25⁺ and CD20⁺ markers. We selected 50 patients who underwent total or partial thyroidectomy in a tertiary service between 1996 and 2013 due to GD with histopathological confirmation. The control group (non-autoimmune disease group) consisted of 12 patients with histopathological data compatible with normal perilesional thyroid parenchyma. The intensity of lymphocytic infiltrate and immunohistochemical expression of the markers CD4⁺ (helper T lymphocytes), CD8⁺ (cytotoxic T lymphocytes), CD25⁺ (regulatory T lymphocytes) and CD20⁺ (B lymphocytes) were retrospectively evaluated and relationship with ultrasound, laboratory and clinical data was assessed.

Results

No differences were found in intensity, presence of lymphoid follicles, and expression of CD4+/CD8+/CD25+ in patients with GD who did or did not use ATD or iodide. In the group that did not use ATD, a higher proportion of CD20⁺ expression was found. The GD group was associated with hyperplastic epithelium and the control group was associated with simple epithelium. There was no difference in ultrasound thyroid volume between the groups. In GD patients with mild lymphocytic infiltrate, higher free thyroxin (FT4) levels were observed than those in patients with no infiltrate or moderate infiltrate.

Conclusion

We found a lower proportion of intrathyroidal CD20⁺ B lymphocytes in patients under use of methimazole. However, no difference was observed in intrathyroidal lymphocyte subpopulations related to the short-term use of iodide. The understanding of thyroid autoimmunity, as well as identifying points of pharmacological modulation, are very important for advancement and improvement in treatments for these diseases.

Pulmonary arterial hypertension (PAH) is characterised by an increase in mean pulmonary arterial pressure and a compromised the right ventricle (RV), together with progression to heart failure and premature death. Studies have evaluated the role of melatonin as a promising therapeutic strategy for PAH. The objective of this study was to evaluate melatonin's effects on oxidative stress and on the TLR4/NF-kβ inflammatory pathway in the RV of rats with PAH. Male Wistar rats were divided into the following groups: control, monocrotaline (MCT), and monocrotaline plus melatonin groups. These two last groups received one intraperitoneal injection of MCT (60 mg/kg) on the first day of experimental protocol. The monocrotaline plus melatonin group received 10 mg/kg/day of melatonin by gavage for 21 days. Echocardiographic analysis was performed, and the RV was collected for morphometric analysis oxidative stress and molecular evaluations. The main findings of the present study were that melatonin administration attenuated the reduction in RV function that was induced by monocrotaline, as assessed by TAPSE. In addition, melatonin prevented RV diastolic area reduction caused by PAH. Furthermore, animals treated with melatonin did not show an increase in ROS levels or in NF-kβ expression. In addition, the monocrotaline plus melatonin group showed a reduction in TLR4 expression when compared with control and monocrotaline groups. To our knowledge, this is the first study demonstrating a positive effect of melatonin on the TLR4/NF-kβ pathway in the RV of rats with PAH. In this sense, this study makes it possible to think of melatonin as a possible ally in mitigating RV alterations caused by PAH.

Parathyroid carcinoma (PCA) is a rare malignancy accounting for approximately 1% of all patients with primary hyperparathyroidism. It is characterised by excessive parathyroid hormone (PTH) production. This manuscript reviews recent advances in the management of parathyroid carcinoma, focusing on molecular insights, diagnostic modalities, surgical innovations, adjuvant therapies, and emerging targeted treatments. Recently published manuscripts (between 2022 and 2023) were obtained from Medical Literature Analysis and Retrieval System Online (Medline), Excerpta Medica (Embase), Cochrane Central Register of Controlled Trials (CENTRAL), and European Union Drug Regulating Authorities Clinical Trials (EudraCT). These were assessed for their relevance in terms of the diagnosis and management of patients with PCA. This manuscript explores the role of genetic profiling and presents case studies illustrating successful management strategies. The manuscript also discusses the ongoing challenges in the management of parathyroid carcinoma, suggesting future research directions and potential therapeutic avenues.

Osteoporosis is the most common metabolic bone disorder and is associated with a high incidence of fractures. Angiogenesis and adequate blood flow are important during bone repair and maintenance. Estrogens play a key role in bone formation, in the prevention of bone resorption and vasculature maintenance. Hormone replacement therapy (HRT) has been used with great benefits for bone fracture prevention but has been linked to the development of serious important side effects, including cancer and stroke. Phytoestrogens are an attractive alternative to HRT because their chemical structure is similar to estradiol but, they could behave as selective modulators: acting as antagonists of estrogen receptors in the breast and endometrium and as agonists in the vascular endothelium and bone. Hops contain a wide variety of phytoestrogens that have individually been shown to possess estrogenic activity by either blocking or mimicking. In this study we have to evaluate the in vitro effects and mechanisms of action of hops extracts on the osteogenic and adipogenic capacity of bone marrow progenitor cells (BMPCs), and the angiogenic potential of EA.hy926 endothelial cells. We show that hops extracts increase the proliferative capacity of BMPCs and promote their osteogenic differentiation while decreasing their pro-osteoclastogenic capacity; and that these effects are mediated by the MAPK pathway. Additionally, hops extracts prevent the adipogenic differentiation of BMPCs and promote endothelial cell activity, by mechanisms also partially mediated by MAPK.

This study addresses the increasing prevalence of obesity, especially among postmenopausal. Estrogen plays a crucial role in regulating adipose tissue in women, with its absence after menopause associated with metabolic complications. The study aimed to determine the lipolytic activity in different adipose tissue depots of ovariectomized rats submitted to a high-fat diet. Also, to analyze the expression of estrogen receptors in adipose tissues and perform histological and morphometric analyzes of these deposits. Female rats were ovariectomized (O) or sham operated (S). The animals were divided into groups: ovariectomized with high-fat diet (OF), sham-operated with high-fat diet (SF), ovariectomized with control diet (OC) or sham-operated with control diet as the control group (SC). After 24 weeks of consuming the diets, rats were killed and adipose tissue deposits were removed. Polymerase chain reaction was performed to analyze the expression of estrogen receptors in adipose tissues, lipolysis assay and histological analysis. Both the high-fat diet and ovariectomy increased body weight and adiposity. There was hypertrophy of adipocytes. Estrogen replacement therapy modulate lipolytic activity in different adipose depots, with different responses in relation to estrogen receptors. Estrogen receptor expression varied between fat depots. Mesenteric adipose tissue showed greater sensitivity to estrogen compared with others. Estrogen increased lipolytic activity in some fat depots, reducing in others. Expression of ERs depends of hormonal status and adipose tissue location, which may explain distinct actions of estrogen on the metabolism of adipose tissue and on the production of adipokines by them.

Activin E activates brown and beige adipocytes and has been controversially implicated as a factor that induces obesity and fatty liver. Here, we sought to address this controversial issue by producing recombinant human activin E to evaluate its effects on HB2 brown adipocytes in vitro. Activin E increased uncoupling protein 1 (Ucp1) and fibroblast growth factor 21 (Fgf21) mRNA expression in the adipocytes. This upregulation was suppressed by SB431542, an inhibitor of activin receptor-like kinase (Alk) TGF-β type I receptors. SB431542 also inhibited the activin E-induced phosphorylation of Smad2/3. A promoter assay using a CAGA-Luc reporter and Alk expression vectors revealed that activin E activated the TGF-β/activin pathway via Alk7. The upregulation of Ucp1 and Fgf21 mRNA might be mediated through Alk7 and Smad2/3 phosphorylation. Activin E is a potential stimulator of energy expenditure by activating brown adipocytes and highlights its potential as a therapeutic target for treating obesity.