Search Results (34)

The approaches to correct thyroid deficiency include replacement therapy with thyroid hormones (THs), but such therapy causes a number of side effects. A possible alternative is thyroid-stimulating hormone (TSH) receptor activators, including allosteric agonists. The aim of this work was to study the effect of ethyl-2-(4-(4-(5-amino-6-(tert-butylcarbamoyl)-2-(methylthio)thieno[2,3-d]pyrimidin-4-yl)phenyl)-1H-1,2,3-triazol-1-yl) acetate (TPY3m), a TSH receptor allosteric agonist developed by us, on basal and thyroliberin (TRH)-stimulated TH levels and the hypothalamic-pituitary-thyroid (HPT) axis in male rats with high-fat diet/low-dose streptozotocin-induced type 2 diabetes mellitus (T2DM). Single and three-day administration of TPY3m (i.p., 20 mg/kg) was studied, and the effect of TPY3m on the HPT axis was compared with that of levothyroxine. TPY3m increased TH levels when administered to both healthy and diabetic rats, normalizing thyroxine and triiodothyronine levels in T2DM and, unlike levothyroxine, without negatively affecting TSH levels or the expression of hypothalamic and pituitary genes responsible for TSH production. TPY3m pretreatment preserved the stimulatory effects of TRH on TH levels and thyroid gene expression. This indicates the absence of competition between TPY3m and endogenous TSH for TSH receptor activation and is supported by our in vitro results on TPY3m- and TSH-stimulated adenylate cyclase activity in rat thyroid membranes. Morphological analysis of thyroid glands in diabetic rats after three-day TPY3m administration shows an increase in its functional activity without destructive changes. To summarize, TPY3m, with the activity of a partial allosteric agonist of the TSH receptor, was created as a prototype of drugs to correct thyroid insufficiency in T2DM. Full article

Radiofrequency electromagnetic fields (RF-EMFs) can penetrate tissues and potentially influence endocrine and brain development. Despite increased mobile phone use among children and adolescents, the long-term effects of RF-EMF exposure on brain and endocrine development remain unclear. This study investigated the effects of long-term evolution band (LTE) EMF exposure on thyroid hormone levels, crucial for metabolism, growth, and development. Four-week-old male mice (C57BL/6) were exposed to LTE EMF (whole-body average specific absorption rate [SAR] 4 W/kg) or a positive control (lead; Pb, 300 ppm in drinking water) for 4 weeks. Subsequently, the mice underwent behavioral tests including open field, marble burying, and nest building. Blood pituitary and thyroid hormone levels, and thyroid hormone-regulating genes within the hypothalamus–pituitary–thyroid (HPT) axis were analyzed. LTE exposure increased T3 levels, while Pb exposure elevated T3 and T4 and decreased ACTH levels. The LTE EMF group showed no gene expression alterations in the thyroid and pituitary glands, but hypothalamic Dio2 and Dio3 expressions were significantly reduced compared to that in the sham-exposed group. Pb exposure altered the hypothalamic mRNA levels of Oatp1c1 and Trh, pituitary mRNA of Trhr, and Tpo and Tg expression in the thyroid. In conclusion, LTE EMF exposure altered hypothalamic Dio2 and Dio3 expression, potentially impacting the HPT axis function. Further research is needed to explore RF-EMF’s impacts on the endocrine system. Full article

Introduction/Aim: Central sensitivity to thyroid hormones refers to the responsiveness of the hypothalamic–pituitary–thyroid (HPT) axis to changes in circulating free thyroxine (fT4). Although dose–response relationships between thyroid hormones per se and urinary iodine (UI) levels have been observed, central sensitivity to thyroid hormones in relation to UI remains unexplored. The aim of the present study was to evaluate central sensitivity to thyroid hormones (by means of the Thyroid Feedback Quantile-based Index [TFQI], which is a calculated measure, based on TSH and fT4, that estimates central sensitivity to thyroid hormones) in pregnancy and to assess whether it differs according to gestational age and/or iodine intake. Materials and Methods: One thousand, one hundred and two blood and urine samples were collected from pregnant women (with a mean age ± SD of 30.4 ± 4.6 years) during singleton pregnancies; women with known/diagnosed thyroid disease were excluded. Specifically, TSH and fT4, anti-thyroid peroxidase antibodies and UI were measured in each trimester and at two months postpartum, while the TFQI was calculated for all the study samples. After the elimination of outliers, statistical analysis was conducted with analysis of variance (ANOVA) for the variables versus time period, while Pearson’s correlation was used to assess the TFQI versus UI. Results: The mean TFQI index ranged from −0.060 (second trimester) to −0.053 (two months postpartum), while the corresponding UI was 137 and 165 μg/L, respectively. The TFQI-UI correlation was marginally negative (Pearson r: −0.323, p: 0.04) and significantly positive (r: +0.368, p: 0.050) for UI values over 250 μg/L, in the first and the second trimesters of pregnancy, respectively. Discussion: The TFQI is a new index reflecting central sensitivity to thyroid hormones. A lower TFQI indicates higher sensitivity to thyroid hormones. In our sample, the TFQI was mainly positively related to iodine intake in the second trimester of pregnancy (following the critical period of organogenesis). Thus, the observed changes in the TFQI may reflect the different ways of the central action of thyroid hormones, according to the phase of pregnancy. These results have the potential to enhance our comprehension of the changes in the HPT axis’ function via variations in central sensitivity to thyroid hormones and its interplay with nutritional iodine status during pregnancy. Full article

Thyroid cancer usually begins with thyroid dysfunction and nodules and has become the most common cancer globally, especially in women. Although the causes of thyroid dysfunction are complex, the presence of environmental pollutants, especially certain pesticides as established mutagens, has been widely accepted. Zebrafish (Danio rerio) have similar toxic reactions and signal transduction pathways to humans and are very similar to humans in physiology, development, and metabolic function. Here, the direct toxicity effects and mechanisms of different insecticides and herbicides on zebrafish thyroid functions and indirect toxicity effects originating from thyroid dysfunction were summarized and compared. The overall toxicity of insecticides on the zebrafish thyroid was greater than that of herbicides based on effective concentrations. Penpropathrin and atrazine were more typical thyroid disruptors than other pesticides. Meanwhile, chiral pesticides showed more sophisticated single/combined toxicity effects on both parental and offspring zebrafish. Besides thyroid hormone levels and HPT axis-related gene expression alteration, developmental toxicity, immunotoxicity, and oxidative damage effects were all observed. These data are necessary for understanding the thyroid interference effect of pesticides on humans and for screening for thyroid disruptors in surface water with zebrafish models for the pre-assessment of human health risks and ecological risk control in the future. Full article

Introduction: Obstructive Sleep Apnea (OSA) in children is characterized by repeated episodes of partial or complete obstruction of the upper airways that impair normal ventilation and cause hypoxia and sleep disruption. These episodes activate innate and adaptive immunity resulting in the production of proinflammatory cytokines: IL-1β, IL-6, TNF-α, and reactive oxygen species. The hypothalamic–pituitary–adrenal (HPT) axis is also activated with alteration of the circadian rhythm of cortisol synthesis. OSA in children, and even more in adults, induces a systemic inflammatory condition that contributes to the genesis of clinical complications: poor growth, learning disabilities, cardiovascular changes, insulin resistance, and metabolic syndrome. Methods: A total of 42 non-obese children (age 1–15 years) were enrolled among those sent to our sleep center to perform full polysomnography (PSG). After PSG, 6 children did not show OSA (controls), 20 had mild OSA (m OSA), and 16 had medium-severe OSA (MS OSA). In vitro IL-1β, TNF-α, and serum cortisol levels were measured at 2 and 8 am in the analyzed groups. Results: Cortisol levels did not differ between controls and OSA children. At 2 am, there were no differences between controls and OSA in TNF-α production, whereas at 8 am, TNF-α was reduced in MS-OSA. IL-1β production showed no differences between OSA and controls. Conclusions: In our population, only TNF-α production is suppressed in MS-OSA: this might indicate a role of OSA severity in inducing inflammation. In adults, the phenomenon is more pronounced due to the habitual greater severity/duration of OSA, presence of comorbidities (cardiovascular and metabolic), and different immune system function. Full article

Withania somnifera, also known as Ashwagandha, has been used in traditional medicine for thousands of years. Due to the wide range of its activities, there has been interest in its possible beneficial effects on the human body. It is proved that, among others, Ashwagandha has anti-stress, anti-inflammatory, antimicrobial, anti-cancer, anti-diabetic, anti-obesity, cardioprotective, and hypolipidemic properties. Particularly interesting are its properties reported in the field of psychiatry and neurology: in Alzheimer’s disease, Parkinson’s disease, multiple sclerosis, depression, bipolar disorder, insomnia, anxiety disorders and many others. The aim of this review is to find and summarize the effect that Ashwagandha root extract has on the endocrine system and hormones. The multitude of active substances and the wide hormonal problems faced by modern society sparked our interest in the topic of Ashwagandha’s impact on this system. In this work, we also attempted to draw conclusions as to whether W. somnifera can help normalize the functions of the human endocrine system in the future. The search mainly included research published in the years 2010–2023. The results of the research show that Ashwagandha can have a positive effect on the functioning of the endocrine system, including improving the secretory function of the thyroid gland, normalizing adrenal activity, and multidirectional improvement on functioning of the reproductive system. The main mechanism of action in the latter appears to be based on the hypothalamus–pituitary–adrenal (HPA) axis, as a decrease in cortisol levels and an increase in hormones such as luteinizing hormone (LH) and follicle-stimulating hormone (FSH) in men were found, which results in stress level reduction and improvement in fertility. In turn, other studies prove that active substances from W. somnifera, acting on the body, cause an increase in the secretion of triiodothyronine (T3) and thyroxine (T4) by the thyroid gland and a subsequent decrease in the level of thyroid-stimulating hormone (TSH) in accordance with the hypothalamus–pituitary–thyroid (HPT) axis. In light of these findings, it is clear that Ashwagandha holds significant promise as a natural remedy for various health concerns, especially those related to the endocrine system. Future research may provide new insights into its mechanisms of action and expand its applications in both traditional and modern medicine. The safety and toxicity of Ashwagandha also remain important issues, which may affect its potential use in specific patient groups. Full article

Parabens are classified as endocrine-disrupting chemicals (EDCs) capable of interfering with the normal functioning of the thyroid, affecting the proper regulation of the biosynthesis of thyroid hormones (THs), which is controlled by the hypothalamic–pituitary–thyroid axis (HPT). Given the crucial role of these hormones in health and the growing evidence of diseases related to thyroid dysfunction, this review looks at the effects of paraben exposure on the thyroid. In this study, we considered research carried out in vitro and in vivo and epidemiological studies published between 1951 and 2023, which demonstrated an association between exposure to parabens and dysfunctions of the HPT axis. In humans, exposure to parabens increases thyroid-stimulating hormone (TSH) levels, while exposure decreases TSH levels in rodents. The effects on THs levels are also poorly described, as well as peripheral metabolism. Regardless, recent studies have shown different actions between different subtypes of parabens on the HPT axis, which allows us to speculate that the mechanism of action of these parabens is different. Furthermore, studies of exposure to parabens are more evident in women than in men. Therefore, future studies are needed to clarify the effects of exposure to parabens and their mechanisms of action on this axis. Full article

Humans have lived in a dynamic environment fraught with potential dangers for thousands of years. While fear and stress were crucial for the survival of our ancestors, today, they are mostly considered harmful factors, threatening both our physical and mental health. Trauma is a highly stressful, often life-threatening event or a series of events, such as sexual assault, war, natural disasters, burns, and car accidents. Trauma can cause pathological metaplasticity, leading to long-lasting behavioral changes and impairing an individual’s ability to cope with future challenges. If an individual is vulnerable, a tremendously traumatic event may result in post-traumatic stress disorder (PTSD). The hypothalamus is critical in initiating hormonal responses to stressful stimuli via the hypothalamic–pituitary–adrenal (HPA) axis. Linked to the prefrontal cortex and limbic structures, especially the amygdala and hippocampus, the hypothalamus acts as a central hub, integrating physiological aspects of the stress response. Consequently, the hypothalamic functions have been attributed to the pathophysiology of PTSD. However, apart from the well-known role of the HPA axis, the hypothalamus may also play different roles in the development of PTSD through other pathways, including the hypothalamic–pituitary–thyroid (HPT) and hypothalamic–pituitary–gonadal (HPG) axes, as well as by secreting growth hormone, prolactin, dopamine, and oxytocin. This review aims to summarize the current evidence regarding the neuroendocrine functions of the hypothalamus, which are correlated with the development of PTSD. A better understanding of the role of the hypothalamus in PTSD could help develop better treatments for this debilitating condition. Full article

High-pressure torsion (HPT) is an effective severe plastic deformation method to produce ultrafine-grained (UFG) and nanocrystalline (NC) materials. In the past, most studies have focused on the evolutions in the microstructure, texture and mechanical properties of HPT-deformed materials at peripheral regions. The corresponding evolutions at a special area were observed in this study to reveal the potential plastic deformation mechanism for face-centred cubic (FCC) material with high stacking fault energy. A decreasing trend was found in grain size, and the final grain size was less than 1 μm. However, close observation revealed that the general trend could be divided into different sub-stages, in which grain elongation and grain fragmentation were dominant, respectively. Additionally, microhardness demonstrated a non-linear increase with the development of plastic deformation. Finally, the microhardness reached a high level of ~64 HV. At the early stages of HPT, the C component was transformed into a cube component, suggesting the material flows around the shear plane normal (SPN) axis at these stages. However, finally they will be replaced by ideal simple shear orientations. Full article

Hypothyroidism is a condition where the patient’s thyroid gland cannot produce sufficient thyroid hormones (mainly triiodothyronine and thyroxine). The primary cause of hypothyroidism is autoimmune-mediated destruction of the thyroid gland, referred to as Hashimoto’s thyroiditis. A patient’s desired thyroid hormone concentration is achieved by oral administration of thyroid hormone, usually levothyroxine. Establishing individual levothyroxine doses to achieve desired thyroid hormone concentrations requires several patient visits. Additionally, clear guidance for the dosing regimen is lacking, and significant inter-individual differences exist. This study aims to design a digital automatic dosing algorithm for patients suffering from Hashimoto’s thyroiditis. The dynamic behaviour of the relevant thyroid function is mathematically modelled. Methods of automatic control are exploited for the design of the proposed robust model-based levothyroxine dosing algorithm. Numerical simulations are performed to evaluate the mathematical model and the dosing algorithm. With the help of the developed controller thyroid hormone concentrations of patients, emulated using Thyrosim, have been regulated under the euthyroid state. The proposed concept demonstrates reliable responses amidst varying patient parameters. Our developed model provides a useful basis for the design of automatic levothyroxine dosing algorithms. The proposed robust feedback loop contributes to the first results for computer-assisted thyroid dosing algorithms. Full article

Dietary regimens that are focused on diminishing total caloric intake and restricting palatable food ingestion are the most common strategies for weight control. However, restrictive diet therapies have low adherence rates in obese patients, particularly in stressed individuals. Moreover, food restriction downregulates the hypothalamic–pituitary–thyroid axis (HPT) function, hindering weight loss. Intermittent fasting (IF) has emerged as an option to treat obesity. We compared the effects of IF to an all-day feeding schedule on palatable diet (PD)-stress (S)-induced hyperphagia, HPT axis function, accumbal thyrotropin-releasing hormone (TRH), and dopamine D2 receptor expression in association with adipocyte size and PPARƔ coactivator 1α (PGC1α) and uncoupling protein 1 (UCP1) expression in stressed vs. non-stressed rats. After 5 weeks, S-PD rats showed an increased energy intake and adipocyte size, fewer beige cells, and HPT axis deceleration-associated low PGC1α and UCP1 expression, as well as decreased accumbal TRH and D2 expression. Interestingly, IF reversed those parameters to control values and increased the number of beige adipocytes, UCP1, and PGC1α mRNAs, which may favor a greater energy expenditure and a reduced body weight, even in stressed rats. Our results showed that IF modulated the limbic dopaminergic and TRHergic systems that regulate feeding and HPT axis function, which controls the metabolic rate, supporting this regimen as a suitable non-pharmacologic strategy to treat obesity, even in stressed individuals. Full article

Cardamom seed (Elettaria cardamomum (L.) Maton; EC) is consumed in several countries worldwide and is considered a nutraceutical spice since it exerts antioxidant, anti-inflammatory, and metabolic activities. In obese individuals, EC intake also favors weight loss. However, the mechanism for these effects has not been studied. Here, we identified that EC modulates the neuroendocrine axis that regulates food intake, body weight, mitochondrial activity, and energy expenditure in mice. We fed C57BL/6 mice with diets containing 3%, 6%, or 12% EC or a control diet for 14 weeks. Mice fed the EC-containing diets gained less weight than control, despite slightly higher food intake. The lower final weight of EC-fed mice was due to lesser fat content but increased lean mass than control. EC intake increased lipolysis in subcutaneous adipose tissue, and reduced adipocyte size in subcutaneous, visceral, and brown adipose tissues. EC intake also prevented lipid droplet accumulation and increased mitochondrial content in skeletal muscle and liver. Accordingly, fasting and postprandial oxygen consumption, as well as fasting fat oxidation and postprandial glucose utilization were higher in mice fed with EC than in control. EC intake reduced proopiomelanocortin (POMC) mRNA content in the hypothalamic arcuate nucleus, without an impact on neuropeptide Y (NPY) mRNA. These neuropeptides control food intake but also influence the hypothalamic-pituitary-thyroid (HPT) and hypothalamic-pituitary-adrenal (HPA) axes. Thyrotropin-releasing hormone (TRH) mRNA expression in the hypothalamic paraventricular nucleus (PVN) and circulating triiodothyronine (T₃) were lower in EC-fed mice than in control. This effect was linked with decreased circulating corticosterone and weight of adrenal glands. Our results indicate that EC modulates appetite, increases lipolysis in adipose tissue and mitochondrial oxidative metabolism in liver and skeletal muscle, leading to increased energy expenditure and lower body fat mass. These metabolic effects were ascribable to the modulation of the HPT and HPA axes. LC-MS profiling of EC found 11 phenolic compounds among which protocatechuic acid (23.8%), caffeic acid (21.06%) and syringic acid (29.25%) were the most abundant, while GC-MS profiling showed 16 terpenoids among which costunolide (68.11%), ambrial (5.3%) and cis-α-terpineol (7.99%) were identified. Extrapolation of mice-to-human EC intake was performed using the body surface area normalization equation which gave a conversion equivalent daily human intake dose of 76.9–308.4 mg bioactives for an adult of 60 kg that can be obtained from 14.5–58.3 g of cardamom seeds (18.5–74.2 g cardamom pods). These results support further exploration of EC as a coadjuvant in clinical practice. Full article

Cadmium (Cd²⁺) and mercury (Hg²⁺) are two kinds of non-essential heavy metals. Cd²⁺ and Hg²⁺ can cause thyroid disruption, but very few researchers have investigated the thyroid-disrupting effects of these metals on fish, specifically during their early developmental transition stage from embryos to larvae. In this study, wild-type zebrafish embryos were exposed to varying concentrations (contents) of Cd²⁺ (0, 10, 100, and 1000 μg/L) and Hg²⁺ (0, 0.1, 1, and 10 μg/L) for 120 h. Thereafter, the thyroid hormone contents and transcriptional changes in the genes, including thyroid stimulating hormone-β (tshβ), thyroglobulin (tg), sodium-iodide symporter (nis), thyroid peroxidase (tpo), transthyretin (ttr), thyroid hormone receptor-α and -β (thrα, thrβ), types I and II iodothyronine deiodinase (dio1, dio2), and uridine diphosphate glucuronosyltransferase 1 family a, b (ugt1ab) associated with the hypothalamic-pituitary-thyroid (HPT) axis were measured. Results showed that zebrafish embryos/larvae malformation rates were significantly higher in the Cd²⁺ and Hg²⁺ groups. A significant increase in the thyroxine (T4) concentration and a decrease in the triiodothyronine (T3) concentration were observed in the Cd²⁺-exposed zebrafish embryos/larvae. On the other hand, the T4 and T3 concentrations were observed to be significantly increased after Hg²⁺ exposure. Additionally, changes were noted in the expression patterns of the HPT axis-linked genes after Cd²⁺ and Hg²⁺ exposure. Based on the results of the principal component analysis (PCA), it was concluded that Cd²⁺ exposure significantly affected the thyroid endocrine system at a concentration of 100 μg/L, whereas Hg²⁺ exposure led to a thyroid disruption at a low concentration of 0.1 μg/L. Thus, this study demonstrated that exposure to Cd²⁺ and Hg²⁺ metal ions induced developmental toxicity and led to thyroid disruption in zebrafish embryos/larvae. Full article

Copper (Cu²⁺) and zinc (Zn²⁺) are two kinds of heavy metals essential to living organisms. Cu²⁺ and Zn²⁺ at excessive concentrations can cause adverse effects on animals, but little is known about the thyroid-disrupting effects of these metals in fish, especially in the early developmental transition stage from embryos to larvae. Wild-type zebrafish embryos were used to expose to Cu²⁺ (0, 1.5, 15, and 150 μg/L) and Zn²⁺ (0, 20, 200, and 2000 μg/L) for 120 h. Thyroid hormone contents and transcriptional changes of the genes connected with the hypothalamic-pituitary-thyroid (HPT) axis were measured. Results showed that zebrafish embryos/larvae malformation rates were significantly increased in the Cu²⁺ and Zn²⁺ groups. Remarkably elevated thyroxine (T4) concentrations and reduced triiodothyronine (T3) concentrations were observed in Cu²⁺ and Zn²⁺ exposure fish. And the expression patterns of genes connected with the HPT axis were changed after Cu²⁺ and Zn²⁺ treatment. Based on principal component analysis (PCA) results, Zn²⁺ caused significant effects on the thyroid endocrine system at 200 μg/L, while Cu²⁺ resulted in thyroid disruption as low as 1.5 μg/L. In short, our study demonstrated that exposure to Cu²⁺ and Zn²⁺ induced developmental toxicity and thyroid disruption to zebrafish embryos/larvae. Full article

The hypothalamic–pituitary–thyroid (HPT) axis is crucial in regulating thyroid hormone levels that contribute to the development and homeostasis of the human body. Current literature supports the presence of a local HPT axis equivalent within keratinocytes of the skin, with thyroid hormones playing a potential role in cancer progression. However, this remains to be seen within oral tissue cells. An electronic search of Scopus and PubMed/Medline databases was conducted to identify all original publications that reported data on the production or effects of HPT axis components in normal or malignant cells of the oral cavity. The search identified 221 studies, of which 14 were eligible. Eight studies were retrospective analyses of clinical samples, one study involved both in vivo and in vitro experiments, and the remaining five studies were conducted in vitro using cell lines. The search identified evidence of effects of HPT components on oral cancer cells. However, there were limited data for the production of HPT axis components by oral tissues. We conclude that a possible role of the local HPT axis equivalent in the oral mucosa may not be established at present. The gaps in knowledge identified in this scoping review, particularly regarding the production of HPT components by oral tissues, warrant further investigation. Full article