Is the Intrinsic Genomic Activity of Thyroxine Relevant In Vivo? Effects on Gene Expression in Primary Cerebrocortical and Neuroblastoma Cells.

Background: The possibility that the intrinsic genomic activity of thyroxine (T4) is of physiological relevance has been frequently hypothesized. It might explain gene expression patterns in the brain found in type 2-deiodinase (Dio2)-deficient mice. These mice display normal expression of most thyroid hormone-dependent genes, despite decreased brain triiodothyronine (T3).

Hypotonic male infant and MCT8 deficiency - a diagnosis to think about.

Background: Thyroid hormone is crucial in the development of different organs, particularly the brain. MCT8 is a specific transporter of triiodothyronine (T3) hormone and MCT8 gene mutations cause a rare X-linked disorder named MCT8 deficiency, also known as Allan-Herndon-Dudley syndrome, characterized by psychomotor retardation and hypotonia. Typically, elevation of T3 and delayed myelination in cerebral magnetic resonance imaging are found.

Critical role of types 2 and 3 deiodinases in the negative regulation of gene expression by T₃in the mouse cerebral cortex.

Thyroid hormones regulate brain development and function through the control of gene expression, mediated by binding of T(3) to nuclear receptors. Brain T(3) concentration is tightly controlled by homeostatic mechanisms regulating transport and metabolism of T(4) and T(3). We have examined the role of the inactivating enzyme type 3 deiodinase (D3) in the regulation of 43 thyroid hormone-dependent genes in the cerebral cortex of 30-d-old mice.

Thyroid hormone regulation of gene expression in the developing rat fetal cerebral cortex: prominent role of the Ca2+/calmodulin-dependent protein kinase IV pathway.

Thyroid hormones influence brain development through regulation of gene expression mediated by nuclear receptors. Nuclear receptor concentration increases rapidly in the human fetus during the second trimester, a period of high sensitivity of the brain to thyroid hormones. In the rat, the equivalent period is the last quarter of pregnancy.

Importance of monocarboxylate transporter 8 for the blood-brain barrier-dependent availability of 3,5,3'-triiodo-L-thyronine.

Mutations of the gene expressing plasma membrane transporter for thyroid hormones MCT8 (SLC16A2) in humans lead to altered thyroid hormone levels and a severe neurodevelopmental disorder. Genetically engineered defect of the Mct8 gene in mice leads to similar thyroid hormone abnormalities but no obvious impairment of brain development or function. In this work we studied the relative role of the blood-brain barrier and the neuronal plasma cell membrane in the restricted access of T(3) to the target neurons.

Glucose controls multiple processes in Saccharomyces cerevisiae through diverse combinations of signaling pathways.

We have studied how the lack of glucose sensors in the plasma membrane, or of the enzymes Hxk1, Hxk2, Glk1, which catalyze the first intracellular step in glucose metabolism, affect the different responses of Saccharomyces cerevisiae to glucose. Lack of the G-protein-coupled receptor Gpr1 or of Snf3/Rgt2 did not affect glucose repression of different genes or activation by glucose of plasma membrane ATPase, whereas lack of Gpr1 decreased, in an additive manner with lack of Mth1, the degradation of fructose 1,6-bisphosphatase that takes place in the presence of glucose. In an hxk1 hxk2 glk1 strain, unable to phosphorylate glucose, all of these responses to the sugar were suppressed or strongly reduced.

Different signalling pathways mediate glucose induction of SUC2, HXT1 and pyruvate decarboxylase in yeast.

The glucose sensors Gpr1, Snf3 and Rgt2 generate the earliest signals produced by glucose in yeast. We showed that a lack of Gpr1 or Snf3/Rgt2 decreased by twofold the glucose induction of SUC2, but had no effect on the induction of pyruvate decarboxylase (Pdc). The induction of HXT1 was not affected by the absence of Gpr1.

Sampling Saccharomyces cerevisiae cells by rapid filtration improves the yield of mRNAs.

To optimize the recovery of mRNAs extracted from yeast, different methods for sampling the yeast cells have been compared. For Saccharomyces cerevisiae strains growing on gluconeogenic carbon sources (derepressed cells) rapid filtration allowed much higher yields (3-10 fold) than centrifugation at room temperature or at 4 degrees C. Recovery of total RNA was similar with the different procedures.

Xylose and some non-sugar carbon sources cause catabolite repression in Saccharomyces cerevisiae.

Glucose and other sugars, such as galactose or maltose, are able to cause carbon catabolite repression in Saccharomyces cerevisiae. Although glycolytic intermediates have been suggested as signal for repression, no evidence for such a control mechanism is available. The establishment of a correlation between levels of intracellular metabolites and the extent of catabolite repression may facilitate the identification of potential signal molecules in the process.