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Modulation of central glucocorticoid receptors in short- and long-term experimental hypothyroidism

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glucocorticoid receptors, HPA axis, Hypothyroidism

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      Abstract

      Aim: Normal adrenocortical responsiveness to stress involves glucocorticoid negative feedback to terminate hypothalamic-pituitary-adrenal (HPA) axis activation. Hypothyroidism is associated with a centrally mediated adrenal insufficiency associated. The aim of this study was to examine whether this may be explained by a disturbed glucocorticoid feedback through specific brain receptors: the mineralocorticoid (MR) and glucocorticoid receptor (GR). Methods: Cytosolic receptor binding and gene expression was assessed in male Sprague-Dawley rats (350gm) with short- (7 days) and long-standing (60 days) hypothyroidism (thyroidectomy). Glucocorticoid receptor number and binding affinity in the hippocampus were measured using radioreceptor assay. In situ hybridization was employed to examine GR and MRmRNA levels in the hippocampus and the pituitary. Results: No differences in receptor number or affinity were observed after 7days and 60days treatment. Increased GRmRNA expression in the anterior pituitary was observed in 7day hypothyroid rats under basal conditions compared to euthyroid rats (122.77+4.93 vs 99.65+4.83 DPM/mg; p<0.05), which was associated with significantly decreased GRmRNA levels after osmotic stress (100.82+2.8 vs 110.48+4.1 DPM/mg; p<0.05). No differences were observed at 60days. No effect on MR mRNA expression in the hippocampus was seen in basal condition after both 7- and 60days hypothyroidism. MRmRNA was significantly decreased in 60 days-hypothyroid rats compared to euthyroid after normal saline (3995.67+131.54 vs 5121.00+505.2 DPM/mg; p<0.05). Conclusion: Hypothyroidism resulted in significant changes in GR and MR mRNA levels, in the hippocampus and the pituitary, without changes in receptor number and binding affinity.

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      Journal
      10.14293/P2199-8442.1.SOP-LIFE.PZX2TI.v1

      Neurosciences

      glucocorticoid receptors, HPA axis, Hypothyroidism

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