Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.1.27.4 (ribonuclease)
 6,621 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Impairment of growth is a hallmark of hypothyroidism in animals. The ability of the thyroid hormone-thyroid hormone receptor complex to regulate gene transcription may be relevant to the growth impairment associated with hypothyroidism. To study the role of thyroid hormone in the expression of the GH receptor (GHR) and GH-binding protein (GHBP) gene, we examined the serum and liver tissue of female and male hypothyroid (thyroidectomized), thyroxine-treated thyroidectomized and euthyroid control rats. Compared to the control and to the thyroxine-treated group, the hypothyroid rats had significantly lower serum levels of thyroxine, increased levels of TSH, and decreased rates of weight gain. GHR and GHBP mRNA levels in liver were estimated by ribonuclease protection assays. In female rats, the levels of hepatic GHR and GHBP mRNA were increased in the hypothyroid group compared to euthyroid controls (p < 0.001 for GHR and p < 0.05 for GHBP). In contrast, in males the hypothyroid state was associated with decreased levels of GHR (p < 0.001) and GHBP (p < 0.001) mRNA levels compared to euthyroid controls. In both females and males, administration of thyroxine for a period of 2 weeks to the thyroidectomized rats prevented these changes in GHR and GHBP mRNA levels in liver. The differences observed between females and males could not be attributed to differences in the circulating levels of GH at sacrifice (female vs. male. 9.9 +/- 1.3 vs. 13.9 +/- 6.5 ng/ml). We conclude that (1) thyroid hormone affects the transcription of the GHR/GHBP gene; (2) there is a distinct sexual dimorphism in the effect of hypothyroidism on the expression of the GHR/GHBP gene, and (3) this effect is reversible following amelioration of the hypothyroid state. We speculate that regulation of expression of the GHR/GHBP gene by thyroid hormones involves multiple thyroid response elements that have opposite effects depending on the status of other factors such as sex hormones.
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PMID:Distinct sexual dimorphism in the effect of hypothyroidism on the expression of the growth hormone receptor and growth hormone-binding protein gene in rat liver. 879 21

Hypothyroidism has devastating consequences on brain development. While the mechanisms that mediate these effects are not known, several lines of evidence suggest that a reduction in insulin-like growth factor-I (IGF-I) expression and/or action has a role. To assess whether reduced IGF-I expression and/or actions mediates the brain pathology of congenital hypothyroidism, we induced hypothyroidism by treating pregnant mice and lactating dams with 0. 1% propylthiouracil (PTU) in drinking water. Control and PTU-treated pups were sacrificed on postnatal day (P) 7, 10 and 14, and IGF-I mRNA expression was assessed in the cerebral cortex and cerebellum by ribonuclease protection assay. To control for mRNA loading, the signal of IGF-I protected bands was normalized to those for cyclophillin. IGF-I mRNA expression in hypothyroid animals was decreased significantly in cortex at P10 and P14 (42 and 60%, respectively). In the cerebellum, IGF-I mRNA expression was down-regulated at all ages studied, but the decrease was only statistically significant at P7 (31% decreased). We conclude that hypothyroidism alters IGF-I expression in the developing brain. Furthermore, we speculate that IGF-I plays a role in mediating some thyroid hormone actions during brain development.
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PMID:Effects of hypothyroidism on insulin-like growth factor-I expression during brain development in mice. 1102 43

The tricarboxylate carrier (TCC), also known as citrate carrier, is an integral protein of the mitochondrial inner membrane. It is an essential component of the shuttle system by which mitochondrial acetyl-CoA, primer for both fatty acid and cholesterol synthesis, is transported into the cytosol, where lipogenesis occurs. The effect of hypothyroidism on the activity and expression of the hepatic mitochondrial TCC was investigated in this study. TCC activity was significantly decreased in hypothyroid rats as compared with euthyroid animals. This hormone deficiency effect was due to a reduction in the amount of carrier protein, which resulted from a proportionate decrease of the specific mRNA. Hypothyroidism did not influence TCC mRNA stability. On the other hand, nuclear run-on assay revealed that the transcriptional rate of TCC mRNA decreased by approximately 40% in the nuclei from hypothyroid versus euthyroid rats. In addition, the ribonuclease protection assay showed that, in the nuclei of hypothyroid rats, the ratio of mature to precursor RNA decreased, indicating that the splicing of TCC RNA is affected. Furthermore, we found that the ratio of polyadenylated/unpolyadenylated TCC RNA as well as the length of the TCC RNA poly(A) tail were similar in both euthyroid and hypothyroid rats. Thus, the rate of formation of the TCC 3'-end is not altered in hypothyroidism. These results suggest that hypothyroidism affects TCC expression at both the transcriptional and post-transcriptional levels.
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PMID:Hypothyroidism reduces tricarboxylate carrier activity and expression in rat liver mitochondria by reducing nuclear transcription rate and splicing efficiency. 1668 15

Dicer is a type III ribonuclease required for the biogenesis of microRNAs (miRNAs), a class of small non-coding RNAs regulating gene expression at the post-transcriptional level. To explore the functional role of miRNAs in thyroid gland function, we generated a thyrocyte-specific Dicer conditional knockout mouse. Here we show that development and early differentiation of the thyroid gland are not affected by the absence of Dicer, while severe hypothyroidism gradually develops after birth, leading to reduced body weight and shortened life span. Histological and molecular characterization of knockout mice reveals a dramatic loss of the thyroid gland follicular architecture associated with functional aberrations and down-regulation of several differentiation markers. The data presented in this study show for the first time that an intact miRNAs processing machinery is essential for thyroid physiology, suggesting that deregulation of specific miRNAs could be also involved in human thyroid dysfunctions.
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PMID:The microRNA-processing enzyme Dicer is essential for thyroid function. 2213 22