Thyroid hormones are essential for the correct development and function of the brain. Their incorrect regulation has been associated with emotional disorders such as anxiety and depression; however, the exact mechanism by which thyroid disfunction contributes to these conditions is not known accurately. On the other hand, oxytocin is a neurohormone synthesised in the brain, specifically in two hypothalamic nuclei, and it has not only peripheral, but also central functions. When released in the brain, it acts as a neurotransmitter, regulating complex processes, including social interaction and emotional response. Interestingly, in the 90s it was discovered that thyroid hormones can regulate the transcription of the oxytocin gene, establishing a connection between both hormones. Despite the relevance of these findings, this field of research has not been further explored. Therefore, the aim of this study is to explore the role of thyroid hormone in regulating the synthesis of oxytocin in thyroid deficient murine models. The experimental model consisted on hypothyroid female mice and female knock-out mice for deiodinase type 2, which have a reduced concentration of the genomically active form of thyroid hormone in the brain. By means of immunohistochemical and qPCR techniques, it was observed that hypothyroidism reduces the synthesis and transcription of oxytocin, while it increases the synthesis and transcription of arginine vasopressin, another neurohormone synthesised in the same brain regions as oxytocin. Nevertheless, no significant changes were observed in knock-out models by immunohistochemical experiments. Moreover, on account of immunofluorescence techniques, it was shown that these alterations are not due to a structural remodelling of those brain nuclei in the hypothyroid model, since astrocyte density and synapsis inputs were not modified. RNA-Seq analysis revealed that hypothyroidism affects a great number of genes, disrupting the neuroendocrine function of the cells located in those nuclei. In conclusion, this study suggest that hypothyroidism has a severe effect on the production of oxytocin, decreasing its synthesis and transcription, which could provide new insights into the pathophysiological mechanisms of anxiety and depression.
Thyroid hormones are essential for the correct development and function of the brain. Their incorrect regulation has been associated with emotional disorders such as anxiety and depression; however, the exact mechanism by which thyroid disfunction contributes to these conditions is not known accurately. On the other hand, oxytocin is a neurohormone synthesised in the brain, specifically in two hypothalamic nuclei, and it has not only peripheral, but also central functions. When released in the brain, it acts as a neurotransmitter, regulating complex processes, including social interaction and emotional response. Interestingly, in the 90s it was discovered that thyroid hormones can regulate the transcription of the oxytocin gene, establishing a connection between both hormones. Despite the relevance of these findings, this field of research has not been further explored. Therefore, the aim of this study is to explore the role of thyroid hormone in regulating the synthesis of oxytocin in thyroid deficient murine models. The experimental model consisted on hypothyroid female mice and female knock-out mice for deiodinase type 2, which have a reduced concentration of the genomically active form of thyroid hormone in the brain. By means of immunohistochemical and qPCR techniques, it was observed that hypothyroidism reduces the synthesis and transcription of oxytocin, while it increases the synthesis and transcription of arginine vasopressin, another neurohormone synthesised in the same brain regions as oxytocin. Nevertheless, no significant changes were observed in knock-out models by immunohistochemical experiments. Moreover, on account of immunofluorescence techniques, it was shown that these alterations are not due to a structural remodelling of those brain nuclei in the hypothyroid model, since astrocyte density and synapsis inputs were not modified. RNA-Seq analysis revealed that hypothyroidism affects a great number of genes, disrupting the neuroendocrine function of the cells located in those nuclei. In conclusion, this study suggest that hypothyroidism has a severe effect on the production of oxytocin, decreasing its synthesis and transcription, which could provide new insights into the pathophysiological mechanisms of anxiety and depression. Read More
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