Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.7.48 (transcriptase)
 9,479 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Dysfunction in thyroid regulation can cause menstrual and ovulatory disturbances, the mechanism of which is not clear. The distribution and activity of the thyroid-stimulating hormone (TSHR), and the thyroid hormone receptors (TR) alpha1, alpha2 and beta1 in human ovarian tissue and in granulosa cells was studied using immunohistochemistry, reverse-transcriptase polymerase chain reaction (RT-PCR), quantitative PCR and immunoassays. Strong immunostaining of TSHR, TRalpha1 and TRbeta1 was observed in ovarian surface epithelium and in oocytes of primordial, primary and secondary follicles, with minimal staining in granulosa cells of secondary follicles. Granulosa cells of antral follicles expressed TSHR, TRalpha1 and TRbeta1 proteins. Messenger RNA for all receptors was present in ovarian tissue. Mature human granulosa cells expressed transcripts for 5' deiodinases types 2 and 3, but not type 1, indicating the possibility of conversion of peripheral thyroid hormone thyroxin (T(4)). Granulosa cells stimulated with TSH showed a significant increase in cAMP concentrations after 2 h of culture (P = 0.047), indicating activation through TSHR. Stimulation with T(4) resulted in increased extracellular signal-regulated kinase 1 and 2 activation after 10, 30, 60 min and 24 h. These data demonstrate that TSH and thyroid hormone receptors may participate in the regulation of ovarian function.
 ...
PMID:Receptors for thyroid-stimulating hormone and thyroid hormones in human ovarian tissue. 1929 32

Thyroid stimulating hormone (TSH) is produced by the anterior pituitary and is used to regulate thyroid hormone output, which in turn controls metabolic activity. Currently, the pituitary is believed to be the only source of TSH used by the thyroid. Recent studies in mice from our laboratory have identified a TSHbeta isoform that is expressed in the pituitary, in peripheral blood leukocytes (PBL), and in the thyroid. To determine whether a human TSHbeta splice variant exists that is analogous to the mouse TSHbeta splice variant, and whether the pattern of expression of the splice variant is similar to that observed in mice, PCR amplification of RNAs from pituitary, thyroid, PBL, and bone marrow was done by reverse-transcriptase PCR and quantitative realtime PCR. Human pituitary expressed a TSHbeta isoform that is analogous to the mouse TSHbeta splice variant, consisting of a 27 nucleotide portion of intron 2 and all of exon 3, coding for 71.2% of the native human TSHbeta polypeptide. Of particular interest, the TSHbeta splice variant was expressed at significantly higher levels than the native form or TSHbeta in PBL and the thyroid. The TSHalpha gene also was expressed in the pituitary, thyroid, and PBL, but not the BM, suggesting that the TSHbeta polypeptide in the thyroid and PBL may exist as a dimer with TSHalpha. These findings identify an unknown splice variant of human TSHbeta. They also have implications for immune-endocrine interactions in the thyroid and for understanding autoimmune thyroid disease from a new perspective.
 ...
PMID:A novel thyroid stimulating hormone beta-subunit isoform in human pituitary, peripheral blood leukocytes, and thyroid. 1936 10

The thyroid hormone receptors (TR) have three major isoforms, TRalpha1, TRalpha2, and TRbeta1; these are ligand-dependent nuclear transcription factors. THRB, the gene encoding TRbeta1, is considered a potential cancer suppressor. The mechanism of its inactivation is not yet clear. Aberrant silencing of THRB in breast cancer tissue and plasma by promoter hypermethylation was investigated in the present study. Reverse transcriptase-polymerase chain reaction (RT-PCR) was used to examine THRB mRNA expression in the breast cancer tissues. Methylation-specific polymerase chain reaction (MSP) combined with nested PCR was used to determine the methylation status of the THRB gene promoter region in 40 cancer tissue and 40 plasma samples from breast cancer patients. Methylation status of MSP product in plasma was also evaluated by direct sequencing. The expression of THRB mRNA in breast cancer tissues was lower than that in the normal tissues; hypermethylation was found in 32 of 40 breast cancer tissues (80%) and in 28 of 40 plasma samples (70%). Loss of THRB gene expression was associated with the CpG island hypermethylation of promoter regions. THRB gene CpG island methylation was not related to clinical pathologic parameters. Sequencing results were identical to agarose gel electrophoresis results. The present results indicate that hypermethylation of THRB as an alternative gene silencing mechanism is highly prevalent in breast cancer. Methylated tumor-specific DNA may serve as a plasma biomarker for prognosis in patients with breast cancer.
 ...
PMID:Aberrant methylation of the THRB gene in tissue and plasma of breast cancer patients. 2008 49


<< Previous 1 2