Impact of Thyroid Hormones on Estrogen Receptor α-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area

Faustino, Larissa C.; Gagnidze, Khatuna; Ortiga-Carvalho, Tânia M.; Pfaff, Donald W.

doi:10.1159/000381459

Cited by 13 publications

(5 citation statements)

References 65 publications

(80 reference statements)

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“…A dose-dependent decrease in DII expression was observed in abdominal arteries from HCB-treated rats, which, together with the lower levels of T4 in serum, could be responsible for the decrease in arterial T3 levels. Moreover, it has been widely established that a decrease in T3 causes a reduction in ER expression (Davis et al, 2002;Faustino et al, 2015) which could be in line with the decrease in ER expression observed in this work.…”

Section: Accepted Manuscriptsupporting

confidence: 90%

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

et al. 2018

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Hexachlorobenzene (HCB) is a dioxin-like environmental pollutant, widely distributed in the environment. New research links exposure to high levels of persistent organic environmental toxicants to cardiovascular disease, however little is known about the effect of HCB on vascular function and on blood pressure. The purpose of the present study was to evaluate biochemical and cardiovascular changes resulting from subchronic HCB exposure. Adult female Sprague-Dawley rats were treated with vehicle or HCB (5 or 500 mg/kg b.w) for 45 days. Systolic blood pressure (BP), recorded by tail cuff plethysmography, was significantly increased at 35, 40 and 45 days of 500 mg/kg HCB-treatment. HCB (500 mg/kg) increased arterial thickness, while both 5 and 500 mg/kg HCB decreased proliferating cell nuclear antigen (PCNA) protein levels and cellular nuclei in abdominal aortas indicating a hypertrophic process. Also, aortas from both groups of HCB-treated rats presented higher sensitivity to noradrenalin (NA) and a significant decrease in maximum contractile response. Arteries from 500 mg/kg HCB-treated rats showed a significant increase in the levels of transforming growth factor-β1 (TGF-β1) mRNA and angiotensin II type1 receptor (AT), and a significant decrease in estrogen receptor alpha (ERα), endothelial nitric oxidide synthase (eNOS) protein expression and deiodinase II (DII) mRNA levels. In conclusion, we have demonstrated for the first time that subchronic HCB administration significantly increases BP and alters associated cardiovascular parameters in rats. In addition, HCB alters the expression of key vascular tissue molecules involved in BP regulation, such as TGF-β1, AT1, ERα, eNOS and DII.

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Section: Accepted Manuscriptsupporting

confidence: 90%

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

et al. 2018

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“…Likewise, the histological changes of hypothyroidism ovaries and testes are in agreement with previous reports (Dijkstra et al 1996, Silva et al 2011. The ventromedial hypothalamus neurons are critical hypothalamic nuclei for the integration of energy balance within the reproductive system (Faustino et al 2015, Carmo-Silva & Cavadas 2017, Sá & Fonseca 2017. Pituitary chromophobes represent degranulated chromophils, inactive reserve cells, or the primary stage of the formation of chromophils (Yoshimura et al 1969).…”

Section: Discussionsupporting

confidence: 89%

Pathological changes and oxidative stress of the HPG axis in hypothyroid rat

Wang

et al. 2021

Journal of Molecular Endocrinology

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Hypothyroidism is a common endocrine disease caused by a deficiency of thyroid hormones, which could affect the hypothalamus–pituitary–gonadal (HPG) axis and cause additional severe fertility problems. However, the pathogenesis of abnormal reproductive capacity caused by hypothyroidism and whether there are differences between females and males need more study. Here, we constructed a prolonged neonatal hypothyroid rat model using 6-propyl-2-thiouracil (PTU). H&E staining and RNA-sequencing were performed to detect histopathological and transcriptome changes. Our results indicated the numbers of ventromedial hypothalamus nuclei were increased, and the number of pituitary chromophobes was sharply increased, whereas the proportion of pituitary acidophils and pituitary basophils were obviously reduced. The differentially expressed genes of the HPG axis organs were identified, and different tissues shared similar steroid hormone and oxidative stress-related terms in gene ontology analysis. Weighted gene co-expression network analysis (WGCNA) and differential expression analysis indicated oxidative stress and apoptosis-related genes were more enriched in male hypothyroid pituitaries, whereas the serum levels of growth hormone, follicle stimulating hormone, and luteinizing hormone that were detected by ELISA were also reduced more in male hypothyroid rats, suggesting that prolonged neonatal hypothyroidism may have a more significant impact on male pituitaries. Moreover, the multi-organ oxidative stress in hypothyroid rats was confirmed by the higher expression of oxidative stress-related genes such as the Txnip. The increased level of oxidative stress may have contributed to the histopathological and transcriptome changes of HPG axis organs in the prolonged neonatal hypothyroidism rats, especially in male pituitaries.

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“…Key factors regulating social behaviors are oxytocin (OXT) and arginine vasopressin (AVP) and they have been studied extensively using different animal models Bielsky et al 2005;Choleris et al 2003;Crawley et al 2007;Ferguson et al 2000;Yu et al 2016) (Champagne et al 2001;Pedersen 1997;Pedersen et al 2006) (Bosch & Neumann 2012;Calcagnoli et al 2014a;Calcagnoli et al 2014b;Ferris & Potegal 1988;Pagani et al 2015). In addition, several studies have shown that thyroid hormones are also implicated in the regulation of those neuropeptides and their signaling Adan et al 1993;Burbach et al 1993;Campo Verde Arbocco et al 2015;Ciosek & Drobnik 2004;Dellovade et al 1999;Faustino et al 2015;Vasudevan et al 2001a;Vasudevan et al 2001b). Thus, it is possible that alterations in the determinants of brain thyroid hormone action contribute to social behaviors.…”

mentioning

confidence: 99%

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

Stohn

Martı́nez

Zafer

et al. 2017

Genes Brain and Behavior

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Thyroid hormones regulate many aspects of brain development and function, and alterations in the levels of thyroid hormone action lead to abnormal anxiety-and depression-like behaviors. A complement of factors in the brain function independently of circulating levels of hormone to strictly controlled local thyroid hormone signaling. A critical factor is the type 3 deiodinase (DIO3), which is located in neurons and protects the brain from excessive thyroid hormone. Here, we examined whether a local increase in brain thyroid hormone action secondary to DIO3 deficiency is of consequence for social behaviors. Although we did not observe alterations in sociability, Dio3−/− mice of both sexes exhibited a significant increase in aggression-related behaviors and mild deficits in olfactory function. In addition, 85% of Dio3−/− dams manifested no pup-retrieval behavior and increased aggression toward the newborns. The abnormal social behaviors of Dio3−/− mice were associated with sexually dimorphic alterations in the physiology of oxytocin (OXT) and arginine vasopressin (AVP), 2 neuropeptides with important roles in determining social interactions. These alterations included low adult serum levels of OXT and AVP, and an abnormal expression of Oxt, Avp and their receptors in the neonatal and adult hypothalamus. Our results demonstrate that DIO3 is essential for normal aggression and maternal behaviors, and indicate that abnormal local regulation of thyroid hormone action in the brain may contribute to the social deficits associated with neurodevelopmental disorders.

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Impact of Thyroid Hormones on Estrogen Receptor α-Dependent Transcriptional Mechanisms in Ventromedial Hypothalamus and Preoptic Area

Cited by 13 publications

References 65 publications

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

Environmental pollutant hexachlorobenzene induces hypertension in a rat model

Pathological changes and oxidative stress of the HPG axis in hypothyroid rat

Increased aggression and lack of maternal behavior in Dio3‐deficient mice are associated with abnormalities in oxytocin and vasopressin systems

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