Propylthiouracil-induced hypothyroidism during lactation alters leucine and mannose metabolism in rat cerebellar slices

Müller, Alexandre Pastoris; Longoni, Aline; Farina, Marcelo; Silveira, Clarice Krás Borges da; Souza, Diogo O.; Perry, Marcos Luiz Santos; Assis, Adriano Martimbianco de

doi:10.1258/ebm.2012.012255

Cited by 10 publications

(5 citation statements)

References 39 publications

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“…In addition, some studies found that the reduction in PRL levels caused by PTU-induced hypothyroidism may reduce milk production of lactating mothers, which may cause growth retardation in the pups (Tamásy et al 1984, Hapon et al 2007. Some studies have found that after weaning, the bodyweight of hypothyroid rats that continued to receive PTU did not change between 28 and 40 days (Dussault & Walker 1978, Dijkstra et al 1996, Mendis-Handagama & Ariyaratne 2004, whereas those that no longer received PTU gradually increased weight, and then returned to normal weight after 100 days (Jena et al 2012, Müller et al 2013, Rijntjes et al 2017. Therefore, we suggest that although there was a confounding effect of growth delay before weaning, the growth retardation of neonatal hypothyroidism was mainly due to the decrease in serum GH levels caused by the decreased number of pituitary eosinophils.…”

Section: Discussionmentioning

confidence: 99%

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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Section: Discussionmentioning

confidence: 99%

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

Wang

et al. 2021

Journal of Molecular Endocrinology

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“…The hyperthyroid groups were given (0.0012% w/v) L-Thyroxine in drinking water for 40 days [22] and the hypothyroid groups were given Propylthiouracil (PTU) (0.05% w/v) [23].…”

Section: Methodsmentioning

confidence: 99%

Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction

Farhadi

Dizaye

2019

International Journal of Endocrinology

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Background and Objectives. Thyroid hormones have an important role in the growth and development of various tissues including the kidney, which is the major site of renin release and the consequent angiotensin and aldosterone formation. Therefore any derangement in thyroid function can result in abnormal functioning in the renin-angiotensin-aldosterone system. The current study was undertaken to find the impact of using a direct renin inhibitor (Aliskiren) and an angiotensin-converting enzyme inhibitor (Fosinopril) on the components of the renin-angiotensin-aldosterone system (RAAS) in rats with thyroid dysfunctions. Method. Forty-two male albino rats were divided into three subgroups. First group (6 rats) served as control. Second group (18 rats) served as hyperthyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Third group (18 rats) served as hypothyroid group (6 rats positive control, 6 rats given Aliskiren, and 6 rats given Fosinopril). Induction of hyperthyroidism and hypothyroidism was done through daily oral administration of L-Thyroxine and Propylthiouracil, respectively. On day 40 of the study, the rats were sacrificed and blood was collected for estimation of renin, angiotensin I, angiotensin II, aldosterone, TSH, T3, and T4. The collected blood samples were also used for estimation of levels blood urea, serum creatinine, liver enzymes, and serum electrolytes. Blood pressure and urine collection were done on days 1 and 40. The collected urine was used for estimation of urine flow, sodium excretion, and potassium excretion rates. Results. In hypothyroid induced rats, serum renin level dropped as expected, while the use of Aliskiren and Fosinopril on these hypothyroid rats raised renin level due to the feedback mechanism. Both angiotensin I and II were significantly (P <0.05) lower than normal levels in the hypothyroid rats, unlike the level of aldosterone, which was higher than normal level. There was nonsignificant lowering in BP (systolic, diastolic, and mean BP) in the hypothyroid rats. Treatment of these rats with Aliskiren and Fosinopril did not lower the blood pressure more than normal when compared to the hypothyroid group. The hypothyroid rats also showed a decrease in level of serum creatinine. In hyperthyroid rats, there was a rise in levels of serum renin, angiotensin II, and aldosterone; nevertheless, the increase in angiotensin I level was significant. The use of Aliskiren and Fosinopril increased the level of renin nonsignificantly (decreased angiotensin I significantly). Hyperthyroid rats showed a significant increase in systolic, diastolic, and mean blood pressure. Both Aliskiren and Fosinopril increased urine flow, Na+ excretion, and K+ excretion rates. Aliskiren was better at reducing the high blood pressure. Conclusion. Aliskiren and Fosinopril in hyperthyroid rats decreased serum angiotensin I, angiotensin II, and aldosterone. Blockade of renin and inhibition of angiotensin-converting enzyme both resulted in a rebound increase in level of renin in hypothyroid rats. Aliskiren is better at controlling blood pressure in hyperthyroid rats. Urine flow, sodium excretion, and potassium excretion rates were improved by the use of Aliskiren and Fosinopril in hyperthyroid rats.

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“…Afterwards, the content of the central well was transferred to vials and assayed for radioactivity in a liquid scintillation counter. All results were calculated based on the initial radioactivity in the incubation medium and expressed in pmol/mg of tissue (Müller et al, 2013). …”

Section: Methodsmentioning

confidence: 99%

Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats

et al. 2016

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Diabetes mellitus (DM) causes important modifications in the availability and use of different energy substrates in various organs and tissues. Similarly, dietary manipulations such as high fat diets also affect systemic energy metabolism. However, how the brain adapts to these situations remains unclear. To investigate these issues, control and alloxan-induced type I diabetic rats were fed either a standard or a high fat diet enriched with advanced glycation end products (AGEs) (HAGE diet). The HAGE diet increased their levels of blood ketone bodies, and this effect was exacerbated by DM induction. To determine the effects of diet and/or DM induction on key cerebral bioenergetic parameters, both ketone bodies (β-hydroxybutyric acid) and lactate oxidation were measured. In parallel, the expression of Monocarboxylate Transporter 1 (MCT1) and 2 (MCT2) isoforms in hippocampal and cortical slices from rats submitted to these diets was assessed. Ketone body oxidation increased while lactate oxidation decreased in hippocampal and cortical slices in both control and diabetic rats fed a HAGE diet. In parallel, the expression of both MCT1 and MCT2 increased only in the cerebral cortex in diabetic rats fed a HAGE diet. These results suggest a shift in the preferential cerebral energy substrate utilization in favor of ketone bodies in animals fed a HAGE diet, an effect that, in DM animals, is accompanied by the enhanced expression of the related transporters.

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Propylthiouracil-induced hypothyroidism during lactation alters leucine and mannose metabolism in rat cerebellar slices

Cited by 10 publications

References 39 publications

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

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

Aliskiren, Fosinopril, and Their Outcome on Renin-Angiotensin-Aldosterone System (RAAS) in Rats with Thyroid Dysfunction

Cerebral Ketone Body Oxidation Is Facilitated by a High Fat Diet Enriched with Advanced Glycation End Products in Normal and Diabetic Rats

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