Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.7.6 (RNA polymerase)
 34,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hormones play a role in the regulation of gene expression by inducing changes in enzyme patterns in target cells mediated by the synthesis of specific RNA molecules. Erythropoiesis has been used as a system for studying the molecular mechanism of regulation of gene action by means of two hormones: erythropoietin and testosterone. Experiments designed to correlate the biochemical action of both hormones on rat marrow cells are herein reported. Both factors seems to act at different biochemical and citological levels. Erythropoietin triggers the erythropoietic process acting on the erythropoietin sensitive cells (ESC), in which the hormone induces the synthesis of a high molecular weight RNA, which is the precursor of a functional 9 S messenger RNA. Testosterone seems to act on polychromatophilic erythroblasts, in which the synthesis of ribosomal RNA or its precursor is stimulated. The steroid enhances the nuclear ribonuclease activity, which could represent a control mechanism for the processing (maturation) of high molecular weight RNAs. The incorporation of 3H-GTP and 3H-UTP into RNA by isolated rat bone marrow nuclei is stimulated by erythropoietin and testosterone. Using alpha-amanitine and different ionic strength conditions it was found that erythropoietin enhances preferentially RNA polymerase II activity while testosterone increases RNA polymerase I activity. It is postulated that erythropoietin and testosterone act synergically to create the biochemical machinery for hemoglobin synthesis, the macromolecule that characterizes the erythropoietic process.
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PMID:Hormonal control of gene expression: differential activation of rat bone marrow RNA polymerases by erythropoietin and testosterone. 9 87

The effect of testosterone on transcription was investigated in the uterus of the ovariectomized rat. Testosterone rapidly depressed both RNA polymerase A and B activities for up to 2 h after administration. Thereafter, RNA polymerase A activity increased, reaching control values at 4 h, and remained constant. On the contrary, RNA polymerase B activity remained depressed at 6 and 18 h after the administration of testosterone. The cellular entities or mechanisms which testosterone uses to alter transcription in the cell nucleus remain to be determined.
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PMID:Action of testosterone on RNA synthesis in the rat uterus. 618 10

The cytodifferentiation of stem cells to mature cells in bone marrow is an appropiate system to study biochemical aspects of hormonal action. We have used this system to analyze the way how erythropoietin and testosterone regulate erythropoiesis at the molecular level. Experiments designed to correlate the biochemical action of both hormones and to determine their differential action on rat bone marrow nuclei DNA-dependent RNA polymerases are reported. The effect of both hormones on the synthesis of RNA by isolated nuclei derived from normal rats was studied. Erythropoietin enhances the activity of RNA polymerase type II while testosterone stimulates polymerase type I activity. Gel-electrophoresis analysis of nuclear RNA shows that erythropoietin enhances the synthesis of RNA species with sedimentation coefficients of 30S, 22S, 15S, and 9S. Testosterone stimulates the synthesis of the 28 and 18S RNA as well as 4S RNA. A model is postulated to explain the action of erythropoietin and testosterone on RNA synthesis by isolated rat bone marrow nuclei.
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PMID:Hormonal control of RNA polymerases in rat bone marrow nuclei. The action of erythropoietin and testosterone. 725 8

Testicular androgens induce the proliferation and differentiation of prostatic epithelial cells by regulating the expression of androgen target genes. The use of subtractive hybridization to isolate genes that are differentially expressed during the early phase of androgen-induced prostatic regrowth in castrated mice resulted in identification of the murine caltrin gene. Caltrin messenger RNA (mRNA) was highly expressed in the prostates of intact mice. Five weeks following castration of mice, steady state caltrin mRNA levels were reduced by 70%. Within 12 hours of administration of pharmacological doses of testosterone enanthate, steady state caltrin mRNA levels were elevated and increased to 90% of levels found in intact mice by 24 hours. Reverse transcriptase-polymerase chain reaction analysis of prostate tissue localized caltrin mRNA transcripts to the dorsal but not the ventral or lateral prostate. Within the dorsal prostate, in situ hybridization always localized caltrin mRNAs to the prostatic epithelial cells. Testosterone-induced increases in caltrin mRNA levels were detected prior to S-phase progression and initiation of proliferation in this cell population. Caltrin has been demonstrated previously to function as a calcium transport inhibitor at the plasma membrane. Findings of this study indicate that caltrin is highly expressed and androgen-regulated in the murine prostate, where it is associated with androgen-induced proliferation and differentiation of epithelial cells.
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PMID:Regulation of caltrin mRNA expression by androgens in the murine prostate. 1133 Jun 45

Ectopic production of biologically active glycoprotein hormones other than hCG has been reported in exceptional cases. A 61-yr-old man came to our Unit complaining of weakness, fatigue and reduced libido with erectile dysfunction. There was also a history of polycythemia, known for about 10 yr and never further investigated. The physical examination showed acne and redness of facial skin and upper chest; no other significant abnormalities were detected. Serum levels of LH were very high, whereas alpha-subunit and hCG were only slightly increased. Testosterone and 17beta-estradiol levels were increased too. Abdominal computed tomography (CT) scan revealed a large hypervascularized mass within the pancreatic tail, which was surgically removed by distal splenopancreatectomy. Diffuse immunoreactivity for LH was detected in more than 70% of the tumor cells. The alpha-subunit was also positive, while chorionic gonadotropin had only a focal reactivity. Reverse transcriptase-polymerase chain reaction (RT-PCR) and Southern Blot analysis confirmed the synthesis of LH by the tumor. Four weeks after surgery, serum levels of LH, alpha-subunit, testosterone, hCG and 17beta-estradiol were all undetectable. The redness of facial skin and upper chest had disappeared, but libido was still reduced. At a further control, 3 months after surgery, serum levels of LH, FSH, hCG, alpha-subunit and 17beta-estradiol were all within the normal range, as well as hemoglobin concentration and the red blood cells count. Testosterone was slightly below normal, but the patient reported an increase of libido. This is an unusual case of ectopic secretion of LH from an endocrine tumor of the pancreas.
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PMID:Ectopic secretion of LH by an endocrine pancreatic tumor. 1523 57

There is a striking gender difference in atherosclerotic vascular disease. For decades, testosterone was considered detrimental to the cardiovascular system. Recent studies, however, have presented some alternative results. The aim of this study was to evaluate the effect of testosterone, using physiological and supraphysiological concentrations, on antigen and mRNA levels of tissue plasminogen activator (tPA), plasminogen activator inhibitor type 1 (PAI-1), and tissue factor pathway inhibitor (TFPI) released by human umbilical vein endothelial cells and to investigate the cellular mechanism. Cells within 2-3 passages were cultured in 25 cm(2) flasks or plated onto 96-well plates with a density of about 1 x 10(5) cells/mL as recommended. The cells were incubated in the presence or absence of testosterone (3, 30, 3 x 10(3), 3 x 10(4) nmol/L) for 48 h. Levels of tPA, PAI-1, and TFPI antigen were assayed with ELISA kits. Reverse transcriptase PCR was carried out to detect tPA, PAI-1, and TFPI mRNA levels. Cells were incubated in androgen-receptor antagonist (flutamide 10 micromol/L) or aromatase inhibitor (aminoglutethimide 50 micromol/L) for 3 h, and then the experiments were repeated. Testosterone at a physiologic concentration (30 nmol/L) increased the antigen levels of tPA and TFPI significantly (P < 0.05). However, tPA and TFPI levels were markedly reduced (P < 0.05) at a larger dose (3 x 10(4) nmol/L). On the other hand, PAI-1 antigen levels decreased significantly at the testosterone concentrations ranging from 3 to 3 x 10(4) nmol/L (P < 0.05). The change in the levels of tPA and TFPI were reflected in the corresponding change in mRNA levels. Flutamide attenuated the effect of testosterone at physiological concentration (30 nmol/L). The results demonstrated that testosterone at physiological concentrations may have a beneficial influence on the haemostatic system through enhancement of anticoagulant activity, resulting from stimulation of TFPI and tPA expression and inhibition of PAI-1 secretion by the endothelium.
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PMID:Physiological testosterone stimulates tissue plasminogen activator and tissue factor pathway inhibitor and inhibits plasminogen activator inhibitor type 1 release in endothelial cells. 1753 6