Hypothalamic-pituitary-thyroid Research Articles

Personality and Psychoneuroimmunology: A Systems Biology Perspective.

Research in psychoneuroimmunology (PNI) underscores the intricate connections within the "whole mind-body system." Personality plays a pivotal role, with specific traits linked to stress influencing neural behavior and psychophysiological disorders. Gene expression networks associated with personality affect neuronal plasticity, epigenetic processes, and adaptive behaviors, highlighting the importance of systems biology mechanisms. Systemic inflammation correlates with key personality traits. Understanding the roles of inflammatory and oxidative biomarkers in personality traits and disorders can help identify diagnostic and therapeutic targets for various diseases. Neurobiological features contribute to our understanding of personality disorders and related conditions. Personality traits are linked to distributed neuroendocrine networks, particularly the hypothalamic-pituitary-adrenal (HPA) axis, rather than localized brain areas. Correlations have also been identified between personality traits and thyroid hormones. Disrupted hypothalamic-pituitary-thyroid (HPT) axis functions may be associated with disease severity, depression, and distress, highlighting the need for comprehensive endocrinological and psychopathological evaluations. The gut-brain axis influences personality traits, emotions, stress, and social behaviors. Altered gut microbiota is common in psychiatric conditions, suggesting potential treatments targeting the microbiota. Chronic stress impacts cognitive functions and correlates with personality and mental health, emphasizing the need for comprehensive, multi-dimensional patient profiles for effective prevention and therapy. A biopsychosocial model integrating personality traits will advance personalized and systems medicine.

Assessing plasmatic transport inhibitors of thyroid hormone in mammals in the Xenopus Eleutheroembryonic Thyroid Assay (XETA).

The Xenopus Eleutheroembryonic Thyroid Assay (XETA, OECD TG 248) was established as an alternative to the Amphibian Metamorphosis Assay (AMA, OECD TG 231) for the analysis of (anti-)thyroid activity of chemicals. The XETA is a New Approach Method (NAM) since the embryonic life stages used in the assay are not yet feeding independently, which renders the assay to be considered a non-animal test under many national laws. Physiologically, the used embryos are not fully developed yet, and thus there are limitations to the XETA for detecting certain mechanisms along the hypothalamic-pituitary-thyroid (HPT) axis. However, the plasmatic transport inhibition of thyroid hormone should physiologically be detectable in the XETA but has not yet been sufficiently investigated. Here, we tested three substances that are known, amongst others, to inhibit thyroid hormone transport by competitive binding to transthyretin in mammalian studies, namely pentachlorophenol (PCP), tetrabromo bisphenol A (TBBPA), and mefenamic acid. Following the test guideline, X. laevis eleutheroembryos of Nieuwkoop-Faber stage 45 were exposed for 72h at 21°C in 6-well plates to different concentrations of the test substances. For PCP and TBBPA, the XETA showed a decrease in fluorescence intensity, which would be expected for thyroid hormone transport inhibition amongst other, similar modes of action, while for the lower potency substance mefenamic acid, a trend was visible, but no statistically significant inhibition was detected. Overall, the results indicate that in the XETA, the plasmatic transport inhibition of thyroid hormone should be detectable alongside other inhibitory modes of action on the HPT axis.

Thyroid and growth hormone endocrine disruption and mechanisms of homosalate and octisalate using wild-type, thrαa-/-, and dre-miR-499-/- zebrafish embryo/larvae

Homosalate (HS) and octisalate (OS), which are used in sunscreen for the purpose of blocking ultraviolet rays, are frequently detected in water environment. Although effects on estrogens and androgens have been reported, studies on thyroid and growth hormone endocrine disruption are limited. In the present study, larval mortality was compared in wild-type and two knockout fish (thyroid hormone receptor alpha a knockout (thrαa-/-) and dre-miR-499 knockout (dre-miR-499-/-)) after 96 h of exposure to HS and OS (0, 0.003, 0.03, 0.3, 3, 30 and 300 µg/L). To investigate the mechanisms of thyroid and growth hormone endocrine disruption, we measured the levels of triiodothyronine (T3), thyroxine (T4), thyroid stimulating hormone (TSH), growth hormone (GH), and insulin-like growth factor-1 (IGF-1), and the regulation of representative genes related to the hypothalamus-pituitary-thyroid (HPT) and GH/IGF axis in wild-type zebrafish exposed to target chemicals. The significantly lower larval survival rate of thrαa-/- and dre-miR-499-/- fish exposed to 300 μg/L of HS and OS suggest that thyroid hormone receptors and dre-miR-499 play a crucial role in the toxic effects of HS and OS. The finding of a significant increase in T3 and T4 in zebrafish larvae exposed to HS and OS supports a significant decrease in the crh gene. The reduction of GH and IGF-1 in fish exposed to HS and OS is well supported by the regulation of genes involved in the GH/IGF axis. Our observations suggest that exposure to HS and OS affects not only thyroid hormone receptors and their associated miRNAs, but also the feedback routes of HPT and GH/IGF axes, ultimately leading to growth reduction.

Effects of 4G Long-Term Evolution Electromagnetic Fields on Thyroid Hormone Dysfunction and Behavioral Changes in Adolescent Male Mice.

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.

7951 The Response of HPT Axis & BAT to Cold Exposure Is Delayed in Female Rats Compared to Males

Abstract Disclosure: A. Gutiérrez-Mata: None. L. Jaimes-Hoy: None. I. Sotelo-Rivera: None. F. Romero-Arteaga: None. R.M. Uribe: None. J.L. Charli: None. P. Joseph-Bravo: None. Cold exposure activates the sympathetic nervous system releasing NE in thermogenic brown adipose tissue (BAT) and in parallel, the Hypothalamus-Pituitary-Thyroid (HPT) axis, increasing synthesis and release of hypothalamic-TRH, pituitary-TSH, and thyroid hormones T4 and T3; T4 in concert with NE induce brown adipose tissue (BAT) thermogenesis through stimulation of deiodinase 2 (Dio2), and uncoupling protein 1 (Ucp1) expression. These changes are detected within the first hour in male rats [J Neuroendo 12:861, 2014] while in females, only in ovariectomized [J Neuroendocrinol 21:439, 2009]. Given the thermogenic effect of ovarian hormones, we hypothesized that females could respond to longer exposures. Female Wistar rats were exposed individually to 5°C for 1 to 5h and compared to male’s acute response (15 min to 4h); controls were moved individually to a nearby room at 22°C for similar times. Rats were euthanized by guillotine, rectal temperature was immediately measured, trunk blood collected, serum separated, and tissues kept at -70°C. Hormone concentrations were quantified in serum by RIA and ELISA, and gene expression in paraventricular nucleus (PVN), anterior pituitary (AP), and BAT by RT-PCR or qPCR. Body temperature of cold-exposed males was higher than isolated controls since the first 30min, Trh expression increased at 1h in the paraventricular nucleus (PVN), TSH release from 15 min up to 2 hours, T4 levels peaked until 4h, and T3 increased after 2h as in [Endocrinology 58:140, 1993]; Trhr1 in AP reached its lowest levels at 2h. In BAT, Dio2 expression peaked at 1h and subsequently decreased. Ucp1 increased from 30 min and remained elevated until 4h, Adrb3, and Ppargc1a expressions were highest at 4h. Cold exposure in females decreased body temperature after 4 hours when Trh PVN expression increased and that of TRH receptor 1 (Trhr1) in AP was lowest; TRH degrading enzyme (Trhde) expression peaked after 2h of cold and subsequently decreased at 4h. TSH in serum increased at 2h and then returned to control levels, T4 slightly increased at 3h, and T3 peaked at 5h. Progesterone serum concentration increased from 2h and peaked at 4h. No changes were found in estradiol serum concentration. In BAT, Dio2 expression increased from 2 to 4h, Ucp1 at 3 and 5h while that of β3 adrenergic receptor (Adrb3) decreased at 2h but rose reaching a peak at 4h. In contrast, expression of Pgc1α -the major transcriptional coactivator of Ucp1- rapidly increased (1h) decreasing afterward. The data suggest that when the ambient temperature decreases, the sympathetic system is activated including stimulation of progesterone, and supports a delayed response of female HPT axis to cold exposure, compared to male’s leading to the proposal that when female body temperature diminishes, the HPT axis and thyroid hormone-induced thermogenesis are activated.Funding: DGAPA IN217422, PAEP, CONAHCYT 790605. Presentation: 6/2/2024

8759 Mild Iodine Deficiency During Pregnancy Impairs Hypothalamus-Pituitary-Thyroid Function Programing of the Adult Male Offspring

Abstract Disclosure: M. Oliveira: None. E. Tavares: None. G. Henrique: None. J. Pinto: None. C. Serrano-Nascimento: None. Introduction: Iodine plays a crucial role in the biosynthesis of thyroid hormones and is essential for proper thyroid embryonic development. While severe iodine deficiency during pregnancy and lactation has well-documented deleterious effects, the consequences of mild iodine deficiency (MID) remain not fully understood. MID during pregnancy is a reality in numerous countries, even in regions with seemingly adequate iodine supply in the diet. Previous studies have highlighted the adverse impact of MID on neurological development in offspring, but comprehensive data on thyroid function, particularly in progeny at different developmental stages, are lacking. This study aimed to investigate the repercussions of MID during pregnancy on the programming of thyroid dysfunctions during adulthood. Methods: Female CD1 mice were subjected to iodine-deficient animal chow and iodine-supplemented water, either at normal (NI; 0.2 mg/L) or mild iodine deficiency (MID; 0.8 mg/L) levels during pregnancy. Gene and protein expression in the hypothalamus, pituitary, and thyroid of adult male offspring animals (PND90) were evaluated using qPCR and Western blotting. Additionally, this study explored MID-induced programming of offspring thyroid gene expression through epigenetic mechanisms. Results: Maternal MID exposure led to increased gene and protein expression of thyrotropin-releasing hormone (TRH) and thyroid-stimulating hormone (TSH) in the hypothalamus and pituitary of the offspring animals. Thyroid protein and gene expression of sodium iodide symporter (NIS), TSH receptor (TSHR), thyroid peroxidase (TPO), thyroglobulin (TG), paired box 8 (PAX8), NK2 homeobox 1 (NKX2.1), and monocarboxylate transporter 8 (MCT8) were elevated in the offspring of MID-exposed animals. Epigenetic mechanisms appeared to contribute to the augmented thyroid gene expression in MID-exposed animals, with decreased DNA methyltransferase expression and reduced thyroid DNA global methylation. Additionally, histone 3 hypomethylation and increased acetylation of histones 3 and 4 were observed. Conclusion: The study suggests that MID exposure during pregnancy can be as harmful as severe iodine deficiency in programming the hypothalamus-pituitary-thyroid (HPT) axis, leading to HPT dysfunction during adult life. Consequently, our data suggest that monitoring iodine intake throughout pregnancy is crucial to prevent the occurrence of thyroid disorders in offspring during adulthood. Presentation: 6/1/2024

Dynamic analysis of Hashimoto’s Thyroiditis bio-mathematical model using artificial neural network

This article establishes an efficient solution scheme for a mathematical model of Hashimoto’s Thyroiditis (HT) employing artificial neural networks. HT is an auto-immune disorder hostile to the thyroid follicle cells, effectuating hypothyroid or hyperthyroidism. Under this condition, the thyroid-stimulating hormone (TSH) alters incomparably to the free thyroxine (FT4) interrupts the functioning of the hypothalamus-pituitary-thyroid (HPT) axis, implicating the thyroid follicle cells getting destroyed. We primarily focus on utilizing artificial neural network (ANN) to perform numerical simulations for the system of ordinary differential equations describing the dynamics of an existing 4D model of HT. The presented model comprises four time-dependent variables: TSH, FT4, anti-thyroid antibodies (Ab), and size of the thyroid gland (T). We utilize ND-Solver and ANN scheme in the Mathematica software to acquire the computational data and illustrate thus retrieved results with essential performance plots. Further, mean square error has been considered in validating the proposed ANN-based approach accurately. The plot for training and validation loss exhibits the effectiveness of the proposed methodology, and substantiate that the suggested ANN approach is a good fit for the solving the mathematical model of HT.

Thyroid endocrine disruption effects of OBS in adult zebrafish and offspring after parental exposure at early life stage

As an alternative to perfluorooctane sulfonate, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been widely used and caused ubiquitous water pollution. However, its toxicity to aquatic organisms is still not well known. Therefore, in this study, parental zebrafish were exposed to OBS at environmentally relevant concentrations from ∼ 2 h post-fertilization to 21 days post-fertilization (dpf) in order to investigate the thyroid disrupting effects in F0 adults and F1 offspring. Histopathological changes, such as hyperplasia of thyroid follicular epithelia and colloidal depletion, were observed in F0 adults at 180 dpf. In F0 females, thyroxine (T4) levels were significantly reduced in 30 and 300 μg/L exposure groups, while triiodothyronine (T3) levels were significantly increased in 3 μg/L exposure group. For F0 males, significant increases of T4 and T3 levels were observed, revealing the sex-specific differences after the OBS exposure. The transcription levels of some key genes related to the hypothalamic-pituitary-thyroid (HPT) axis were significantly disrupted, which induced the thyroid endocrine disruption effects in adult zebrafish even after a prolonged recovery period. For F1 offspring, the thyroid hormone (TH) homeostasis was also altered as T4 and T3 levels in embryos/larvae exhibited similar changes as F0 females. The transcription levels of some key genes related to the HPT axis were also significantly dysregulated, suggesting the transgenerational thyroid disrupting effects of OBS in F1 offspring. In addition, the decreased swirl-escape rate was observed in F1 larvae, which could be caused by disrupting gene expressions related to the central nervous system development and be associated with the TH dyshomeostasis. Therefore, parental OBS exposure at early life stage resulted in thyroid endocrine disruption effects in both F0 adult zebrafish and F1 offspring, and caused the developmental neurotoxicity in F1 larvae.

Testing the sensitivity of the medaka Transgenic Eleuthero-embryonic THYroid-Specific assay (TETHYS) to different mechanisms of action

There are many concerns about the impacts of Endocrine-Disrupting Chemicals on both wildlife and human populations. A plethora of chemicals have been shown to interfere with the Hypothalamic–Pituitary–Thyroid (HPT) axis in vertebrates. Disruption of the HPT axis is one of main endocrine criteria considered for the regulation of chemicals, along with the estrogen axis, androgen axis and steroidogenesis (EATS). In response to these concerns, the Organization for Economic Cooperation and Development (OECD) initiated the validation of test guidelines (TGs) covering the EATS modalities. Regarding thyroid activity and/or disruption assessment, three OECD TGs are validated, all of them using amphibians. To date, no OECD TGs based on fish are available for the detection of Thyroid Active Chemicals (TACs). To fill this gap, we developed a new test for the detection of TACs, the TETHYS assay (Transgenic Eleuthero-embryonic THYroid-Specific assay). This assay uses a medaka (Oryzias latipes) transgenic line Tg(tg:eGFP) expressing Green Fluorescent Protein in the thyroid follicles, under the control of the thyroglobulin promoter. This assay is performed at eleuthero-embryonic life-stages with an exposure length of 72 h. In the present study, the following reference chemicals with known thyroid hormone system mechanism of action have been tested: methimazole, sodium perchlorate, sodium tetrafluoroborate, diclofenac, iopanoic acid, sobetirome, NH-3 and 1–850. Except for the thyroid receptor antagonists, all chemicals tested were identified as thyroid active, modifying the total fluorescence and the size of the thyroid follicles. To investigate the test specificity, we tested three chemicals presumed to be inert on the HPT axis: cefuroxime, abamectin and 17α-ethinylestradiol. All were found to be inactive in the TETHYS assay. This promising New Approach Methodology can serve as a foundation for the development of a new OECD TG in the frame of regulatory assessment of chemicals for thyroid activity.

Age-Related Features of the Function of the Hypothalamic-Pituitary-Thyroid (HPT) Axis in Nonhuman Primates under Constant Lighting.

We studied the features of the functioning of the hypothalamic-pituitary-thyroid (HPT) axis under conditions of constant (4 weeks) lighting (LED lamps intended for office and residential premise) on a translational model of young adult and old female rhesus monkeys, in particular taking into account their behavior. Constant lightning had no significant effect on the levels of thyroid-stimulating hormone, thyroxine, and triiodothyronine under basal conditions in all animals, regardless of age and behavioral characteristics, but induced a decrease in thyroid function under conditions of its activation with thyrotropin-releasing hormone, mainly in old animals.

Thyroid Dysfunction and Bipolar Disorder: A Literature Review Integrating Neurochemical, Endocrine, and Genetic Perspectives.

Thyroid disorders are common in medicine, while bipolar disorders (BDs), though less frequent, are significant due toglobal prevalence, the economic burden on healthcare systems and long-term health implications, and the effects ofpsychiatric illness on quality of life. Clinical research has suggested thyroid hormone imbalances can cause psychiatric symptoms similar to the clinical features observed in BDs. Despite increased attention in this area of study, much remains unknown regarding how thyroid issues contribute to the development of BDs. This review explores the complex link between thyroid disorders and BDs, focusing on neurochemical dynamics, changes in the hypothalamic-pituitary-thyroid (HPT) axis, and genetic factors. Furthermore, this literature review examines the importance of understanding these factors in linking both conditions and emphasizes the necessity for therapies targeting their shared underlying mechanisms.

Correction: The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis

Correction: The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis

The Effects of Triiodothyronine on the Free Thyroxine Set Point Position in the Hypothalamus Pituitary Thyroid Axis.

In clinical endocrinology, it is often assumed that the results of thyroid hormone function tests (TFTs) before total thyroidectomy are considered euthyroid when the circulating concentrations of thyrotropin [TSH] and free thyroxine [FT4] are within the normal reference ranges. Postoperative thyroid replacement therapy with levothyroxine. The aim of L-T4 is to reproduce the preoperative euthyroid condition. Currently, intra-individual changes in the euthyroid set point before and after total thyroidectomy are only partly understood. After total thyroidectomy, a greater postoperative [FT4] than preoperative [FT4] for equivalent euthyroid [TSH] was found, with differences ranging from 3 to 8 pmol/L. This unexplained difference can be explained by the use of a mathematical model of the hypothalamus-pituitary-thyroid (HPT) axis set point theory. In this article, the postoperative HPT euthyroid set point was calculated using a dataset of total thyroidectomized patients with at least three distinguishable postoperative TFTs. The postoperative [TSH] set point was used as a homeostatic reference for the comparison of preoperative TFTs. The preoperative [FT4] value was equal to the postoperative [FT4] value in 50% of the patients, divided by a factor of ~ 1.25 (within +/- 10%). The factor of 1.25 stems from the lack of postoperative use of thyroidal triiodothyronine (T3). Furthermore, approximately 25% of the patients presented a greater preoperative [FT4] difference than postoperative [FT4]/1.25 combined with a normal [TSH] difference. Based on these observations, the effect of T3 on the value of the [FT4] set point was analyzed and explained from a control theory perspective.

Perinatal exposure to Aroclor 1254 disrupts thyrotropin-releasing hormone mRNA expression in the paraventricular nucleus of male and female rats

Polychlorinated biphenyls (PCBs) are industrial pollutants that act as endocrine disruptors and alter thyroid function. However, it is still unclear whether PCBs can affect hypothalamic thyrotropin releasing hormone (Trh) mRNA expression through TH signaling disruption. As salt-loading dehydration induces tertiary hypothyroidism in the hypothalamic parvocellular paraventricular nuclei (paPVN), and perinatal exposure to Aroclor 1254 (A1254) disrupts the hydric balance in rats, we hypothesized that TRH synthesis could be altered during dehydration in TRH neurons that control the hypothalamic–pituitary–thyroid (HPT) axis activity in rats perinatally exposed to A1254. We examined Trh mRNA expression in the paPVN and the response to salt-loading dehydration (hyperosmotic (hyper) stress) in the progeny of Wistar pregnant rats receiving 0 mg/kg BW (control) or 30 mg/kg BW A1254 daily from gestational days 10–19. Three-month-old offspring were subjected to normosmotic or hyper conditions and Trh mRNA, glucocorticoid receptor (GR) mRNA expression were measured in the PVN by RT-PCR. TRH mRNA and TRH+ neurons were measured in the paPVN by fluorescent in situ hybridization (FISH). As expected, Trh mRNA levels were decreased in the paPVN of male and female rats in the hyper group. Basal Trh mRNA expression and serum TSH were decreased in male rats in the A1254 group. Notably, Trh mRNA levels were further decreased in the paPVN of male and female A1254 + hyper rats, in which the GR mRNA expression was significantly decreased. These results support the hypothesis that perinatal exposure to A1254 results in inadequate adaptive response of the HPT axis in adulthood and contributes to dysregulation of the HPT axis response to salt-loading dehydration.

The influence of extended fasting on thyroid hormone: local and differentiated regulatory mechanisms.

The hypometabolism induced by fasting has great potential in maintaining health and improving survival in extreme environments, among which thyroid hormone (TH) plays an important role in the adaptation and the formation of new energy metabolism homeostasis during long-term fasting. In the present review, we emphasize the potential of long-term fasting to improve physical health and emergency rescue in extreme environments, introduce the concept and pattern of fasting and its impact on the body's energy metabolism consumption. Prolonged fasting has more application potential in emergency rescue in special environments. The changes of THs caused by fasting, including serum biochemical characteristics, responsiveness of the peripheral and central hypothalamus-pituitary-thyroid (HPT) axis, and differential changes of TH metabolism, are emphasized in particular. It was proposed that the variability between brain and liver tissues in THs uptake, deiodination activation and inactivation is the key regulatory mechanism for the cause of peripheral THs decline and central homeostasis. While hypothalamic tanycytes play a pivotal role in the fine regulation of the HPT negative feedback regulation during long-term fasting. The study progress of tanycytes on thyrotropin-releasing hormone (TRH) release and deiodination is described in detail. In conclusion, the combination of the decrease of TH metabolism in peripheral tissues and stability in the central HPT axis maintains the basal physiological requirement and new energy metabolism homeostasis to adapt to long-term food scarcity. The molecular mechanisms of this localized and differential regulation will be a key research direction for developing measures for hypometabolic applications in extreme environment.

Early-life exposure to five biodegradable plastics impairs eye development and visually-mediated behavior through disturbing hypothalamus-pituitary-thyroid (HPT) axis in zebrafish larvae

Biodegradable plastics have been commonly developed and applied as an alternative to traditional plastics, which cause environmental plastic pollution. However, biodegradable plastics still present limitations such as stringent degradation conditions and slow degradation rate, and may cause harm to the environment and organisms. Consequently, in this study, zebrafish was used to evaluate the effects of five biodegradable microplastics (MPs), polyglycolic acid (PGA), polylactic acid (PLA), polybutylene succinate (PBS), polyhydroxyalkanoate (PHA) and polybutylene adipate terephthalate (PBAT) exposure on the early development, retina morphology, visually-mediated behavior, and thyroid signaling at concentrations of 1 mg/L and 100 mg/L. The results indicated that all MPs induced decreased survival rate, reduced body length, smaller eyes, and smaller heads, affecting the early development of zebrafish larvae. Moreover, the thickness of retinal layers, including inner plexiform layer (IPL), outer nuclear layer (ONL), and retinal ganglion layer (RGL) was decreased, and the expression of key genes related to eye and retinal development was abnormally altered after all MPs exposure. Exposure to PBS and PBAT led to abnormal visually-mediated behavior, indicating likely affected the visual function. All MPs could also cause thyroid system disorders, among which alterations in the thyroid hormone receptors (TRs) genes could affect the retinal development of zebrafish larvae. In summary, biodegradable MPs exhibited eye developmental toxicity and likely impaired the visual function in zebrafish larvae. This provided new evidence for revealing the effects of biodegradable plastics on aquatic organism development and environmental risks to aquatic ecosystems.

Levels of Expression of Hsp70 and iNOS and Effect of Artemisia Sieberi (A. herba-alba) on Activity of Hypothalamic-Pituitary-Thyroid (HPT) Axis in Diabetic Rats

This work was carried out to evaluate levels of expression of the Heat Shock Protein 70 (Hsp70) and inducible nitric oxide synthase (iNOS) biomarkers in extracts of Artemisia sieberi (A. herba-alba) and their impacts on the activity of hypothalamic-pituitary-thyroid (HPT) axis in diabetic rats. 50 rats were separated into five experimental groups: a normal control group, a positive control group treated with dilute A. herba alba (AHE) oil extract, a diabetic non-treated group, a diabetic group treated with AHA extract, and a diabetic group treated with Metformin. Results: Orally administered 8.1 mg/kg body weight (BW) of dilute AHA oil and 14.2 mg/kg BW of Metformin were administered for 6 weeks. Serum triiodothyronine (T3) levels decreased significantly in diabetic rats and increased significantly in the rats treated with the dilute AHA oil. Furthermore, no significant differences were observed in thyroid gland Hsp70 expression between the diabetic and non-diabetic rats. Metformin and dilute AHA oil treatments significantly increased the expression of Hsp70 in the thyroid gland. The results also demonstrated that diabetes significantly increased the rate of iNOS expression in the thyroid gland. Treatment with Metformin and dilute AHA oil significantly reduced the expression of iNOS in the thyroid gland. These results suggest that dilute AHA oil plays a role in the peripheral regulation of thyroid function and provide empirical evidence that it contributes to the stimulation or improvement of thyroid function.

TSH-Receptor-Mediated regulation of thyroid hormones in the hypothalamic-pituitary thyroid axis

TSH-Receptor-Mediated regulation of thyroid hormones in the hypothalamic-pituitary thyroid axis

Intracerebroventricular prokineticin 2 infusion may play a role on the hypothalamus-pituitary-thyroid axis and energy metabolism

AimThe hypothesis of this study is to determine the effects of intracerebroventricular (icv) prokineticin 2 infusion on food consumption and body weight and to elucidate whether it has effects on energy expenditure via the hypothalamus-pituitary-thyroid (HPT) axis in adipose tissue. Material and MethodsA total of 40 rats were used in the study and 4 groups were established: Control, Sham, Prokineticin 1.5 and Prokineticin 4.5 (n=10). Except for the Control group, rats were treated intracerebroventricularly via osmotic minipumps, the Sham group was infused with aCSF (vehicle), and the Prokineticin 1.5 and Prokineticin 4.5 groups were infused with 1.5 nMol and 4.5 nMol prokineticin 2, respectively. Food and water consumption and body weight were monitored during 7-day infusion in all groups. At the end of the infusion, the rats were decapitated and serum TSH, fT4 and fT3 levels were determined by ELISA. In addition, PGC-1α and UCP1 gene expression levels in white adipose tissue (WAT) and brown adipose tissue (BAT), TRH from rat hypothalamic tissue were determined by real-time PCR. ResultsIcv prokineticin 2 (4.5 nMol) infusion had no effect on water consumption but reduced daily food consumption and body weight (p<0.05). Icv prokineticin 2 (4.5 nMol) infusion significantly increased serum TSH, fT4 and fT3 levels when compared to Control and Sham groups (p<0.05). Also, icv prokineticin 2 (4.5 nMol) infusion increased the expression of TRH in the hypothalamus tissue and expression of PGC-1α UCP1 in the WAT and BAT (p<0.05). ConclusionIcv prokineticin 2 (4.5 nMol) infusion may suppress food consumption via its receptors in the hypothalamus and reduce body weight by stimulating energy expenditure and thermogenesis in adipose tissue through the HPT axis.

New insights into the hypothalamic-pituitary-thyroid axis: a transcriptome- and proteome-wide association study.

Thyroid hormones have systemic effects on the human body and play a key role in the development and function of virtually all tissues. They are regulated via the hypothalamic-pituitary-thyroid (HPT) axis and have a heritable component. Using genetic information, we applied tissue-specific transcriptome-wide association studies (TWAS) and plasma proteome-wide association studies (PWAS) to elucidate gene products related to thyrotropin (TSH) and free thyroxine (FT4) levels. TWAS identified 297 and 113 transcripts associated with TSH and FT4 levels, respectively (25 shared), including transcripts not identified by genome-wide association studies (GWAS) of these traits, demonstrating the increased power of this approach. Testing for genetic colocalization revealed a shared genetic basis of 158 transcripts with TSH and 45 transcripts with FT4, including independent, FT4-associated genetic signals within the CAPZB locus that were differentially associated with CAPZB expression in different tissues. PWAS identified 18 and ten proteins associated with TSH and FT4, respectively (HEXIM1 and QSOX2 with both). Among these, the cognate genes of five TSH- and 7 FT4-associated proteins mapped outside significant GWAS loci. Colocalization was observed for five plasma proteins each with TSH and FT4. There were ten TSH and one FT4-related gene(s) significant in both TWAS and PWAS. Of these, ANXA5 expression and plasma annexin A5 levels were inversely associated with TSH (PWAS: P = 1.18 × 10-13, TWAS: P = 7.61 × 10-12 (whole blood), P = 6.40 × 10-13 (hypothalamus), P = 1.57 × 10-15 (pituitary), P = 4.27 × 10-15 (thyroid)), supported by colocalizations. Our analyses revealed new thyroid function-associated genes and prioritized candidates in known GWAS loci, contributing to a better understanding of transcriptional regulation and protein levels relevant to thyroid function.