reproductive cycles and sexual function.Hormones are essential for regulating most major bodily processes, so a hormonal imbalance can affect many bodily functions. Hormones travel through the bloodstream to the tissues and organs, delivering messages that tell the organs what to do and when to do it. Hormones are chemicals produced by glands in the endocrine system. Because of their essential role in the body, even slight hormonal imbalances can cause side effects throughout the body. 10.1038/ imbalances occur when there is too much or too little of a hormone in the bloodstream. Thyroid hormone transporters-functions and clinical implications. Expression profiles of the three iodothyronine deiodinases, D1, D2, and D3, in the developing rat. Fetal and neonatal iron deficiency exacerbates mild thyroid hormone insufficiency effects on male thyroid hormone levels and brain thyroid hormone-responsive gene expression. HTSeq–a Python framework to work with high-throughput sequencing data. We conclude that DIO3 function is critical to ensure an adequate timing for TH action in the developing brain and is probably the main factor underlying the lack of effects on the fetal brain observed in previous studies after TH administration.ĭio3 Klf9 Nrgn brain development thyroid hormone type 3 deiodinase.Īnders S., Pyl P. Overall, our results demonstrate that the rodent fetal brain is sensitive to TH as early as E13.5 of gestational age, and suggest that TH distinctly affects brain developmental programs in early and late gestation. Differential expression at E13.5 was confirmed by qPCR for additional genes related to collagen and extracellular matrix and for selected transcription factors. Although pathway analyses of differentially expressed genes at E13.5 also revealed significant enrichment in axonal guidance and synaptogenesis signaling, top enrichment was found for functions related to the cell cycle, aryl hydrocarbon receptor signaling, PCP and kinetochore metaphase signaling pathways and mitotic roles of polo-like kinase. Differential expression of 13 of these genes, including Klf9, Hr, and Mgp, was confirmed in an extended set of samples including females. Additional RNA sequencing identified 588 genes differentially expressed (35% up-regulated) in the brain of E13.5 Dio3-/- male fetuses.
Pathway analyses of differentially expressed genes indicated enrichment in glycolysis and signaling related to axonal guidance, synaptogenesis and hypoxia inducible factor alpha. Differential expression of 13 of these genes was confirmed in an extended set of samples that included females. RNA sequencing revealed 246 genes differentially expressed (70% up-regulated) in the brain of E18.5 Dio3-/- male fetuses. The increased expression of these genes was confirmed by in situ hydridization in multiple areas of the cortex and in the striatum. At embryonic day E18.5 qPCR determinations indicated a marked increase in the mRNA expression of T3-responsive genes Klf9 and Nrgn. To address this issue, here we examined gene expression in brains from mouse fetuses deficient in the type 3 deiodinase (DIO3), the selenoenzyme responsible for clearing TH. Although their effects on the rodent brain peak within 2-3 weeks postnatally, the fetal brain has been found largely insensitive to exogenously administrated TH. Thyroid hormones (TH) are critical for the development and function of the central nervous system (CNS).
0 kommentar(er)
