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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The expression of insulin receptor mRNA was studied in human and rodent tissues by Northern analysis. Human EBV-transformed lymphocytes contained four receptor mRNA species of sufficient length to encode the entire proreceptor: 9.5, 7.9, 7.1, and 5.7 kb. In human fibroblasts, the same four species were observed; however, the 7.9 and 5.7 kb mRNAs were markedly decreased. In mouse liver, rat hepatoma cells, and normal rat brain, kidney, liver, and muscle only two mRNA species (7.4 and 9.6 kb) were detected. Each of these human and rodent mRNAs hybridized equally well with cDNA sequences encoding the binding and kinase domains of the insulin receptor. Several smaller polyadenylated mRNAs (approximately 1.8 to 3.3 kb) were also identified in human cell lines that appeared to separately encode either alpha- or beta-subunit sequences of the receptor. In rats, liver had the highest content of insulin receptor mRNA, followed by kidney, brain, and muscle. The relative amount of the two mRNA species also varied among the rat tissues. The ratio of the 9.6-7.4 kb species was 2.7 in brain but only 1.0 to 1.6 in the other tissues (P less than 0.025). Dexamethasone treatment increased the content of the two insulin receptor mRNAs in rat liver by 2-fold. The half-life of both mRNA species was 70 min in rat hepatoma cells. These findings indicate that insulin receptor gene expression is complex and regulated with differential expression of insulin receptor mRNA and/or alterations in mRNA processing among various tissues.
Mol Endocrinol 1987 Nov
PMID:Variation in insulin receptor messenger ribonucleic acid expression in human and rodent tissues. 248 15

Primary cultures of rat hepatocytes produce tissue-type plasminogen activator (tPA) and plasminogen activator-inhibitor type 1 (PAI-1). Incubation of hepatocytes with 50 microM 8-(4-chlorophenylthio)cAMP (CPT-cAMP) results in a 4-fold increase in tPA activity, whereas the synthetic glucocorticoid dexamethasone (1 microM) causes a more than 90% decrease. In combination, dexamethasone completely overcomes the CPT-cAMP effect and markedly decreases PA activity. PAI-1 is induced by both CPT-cAMP and dexamethasone, and the effects of these agents are additive. Accumulation of tPA mRNA is increased more than 4-fold by CPT-cAMP and is greatly decreased by incubation with dexamethasone. Dexamethasone in combination with CPT-cAMP totally blocks this cAMP effect. The protein synthesis inhibitor cycloheximide does not prevent either the dexamethasone-induced decrease or the CPT-cAMP-induced increase in tPA message and, in fact, augments the cAMP-induced increase in tPA mRNA. Hepatocyte PAI-1 mRNA levels are increased 2-fold by incubation with either CPT-cAMP or dexamethasone; in combination, these effectors cause a 4-fold increase in PAI-1 mRNA. Cycloheximide alone causes a marked increase in PAI-1 mRNA, but does not block the induction by either CPT-cAMP or dexamethasone. We conclude that incubation of hepatocytes with CPT-cAMP induces tPA activity by increasing tPA mRNA accumulation and that dexamethasone causes a decrease in tPA activity by both decreasing tPA mRNA and increasing PAI-1 mRNA and activity. Concomitant protein synthesis is not required for the regulation of tPA or PAI-1 mRNA by either CPT-cAMP or dexamethasone, indicating a primary effect of these agents on gene transcription or mRNA stability.
Mol Endocrinol 1989 Jan
PMID:Glucocorticoid and cyclic nucleotide regulation of plasminogen activator and plasminogen activator-inhibitor gene expression in primary cultures of rat hepatocytes. 253 89

To clarify the mechanism of growth hormone (GH) gene activation by glucocorticoids in GH3 pituitary cells, GH mRNA accumulation in nuclear and cytoplasmic compartments was measured in the presence and absence of cycloheximide. In dexamethasone-treated cells, levels of GH mRNA were increased in the nucleus by 6 h and in the cytoplasm by 12 h. Dexamethasone treatment caused a 5- to 24-fold rise in total GH mRNA levels by 48-72 h. The differential elevation of nuclear levels of GH mRNA relative to the amount of cytoplasmic GH mRNA persisted for 48 h. A transient accumulation of GH mRNA in the nucleus was followed by a brief rise in cytoplasmic GH mRNA levels in GH3 cells treated simultaneously with dexamethasone and cycloheximide. In GH3 cells pretreated for 2 h with cycloheximide, the rise in nuclear and cytoplasmic GH mRNA levels mediated by dexamethasone was blocked completely. Levels of glucocorticoid receptor were unaffected by cycloheximide. These data suggest that the stimulation of GH mRNA levels by glucocorticoids is initiated within the nucleus and that cycloheximide-sensitive events are essential for this stimulation to occur. To assess the importance of GH gene transcriptional activation by glucocorticoids, nuclear transcription run-on reactions and assays of GH promoter activity in an aminoglycoside 3'-phosphotransferase (Neo) fusion gene within stably transformed GH3 cells were performed. Evidence for a weak, transient transcriptional activation of the GH gene by dexamethasone in nuclear run-on assays was obtained. Consistent with this idea, a 30-72 h exposure to dexamethasone raised levels of Neo mRNA in GH-Neo GH3 cell transformants by less than or equal to 2-fold. We conclude that glucocorticoid stimulation of GH mRNA in GH3 cells requires ongoing protein synthesis and can occur largely independently of GH gene transcriptional activation.
Mol Cell Endocrinol 1989 Sep
PMID:Dexamethasone control of growth hormone mRNA levels in GH3 pituitary cells is cycloheximide-sensitive and primarily posttranscriptional. 258 64

UMR 201 is a nontransformed rat clonal cell line derived from neonatal calvaria with phenotypic characteristics of preosteoblasts. Retinoic acid strongly induces expression of alkaline phosphatase and its mRNA in these cells. Dexamethasone substantially reduced the retinoic acid-induced expression of alkaline phosphatase. This apparent interaction between dexamethasone and retinoic acid effects raised the possibility that interactions may extend to other osteoblast-related phenotypic characteristics in UMR 201 cells. Treatment with dexamethasone resulted in a decrease in the expression of mRNA for pro-alpha 1(I) collagen, but upon coincubation with 1 microM retinoic acid for 24 h, the decrease in mRNA for pro-alpha 1(I) collagen was abrogated. Dexamethasone (Dex) treatment caused a dose-dependent increase in osteonectin mRNA, half maximally effective between 1 nM and 10 nM Dex. One micromolar of retinoic acid alone led to a small increase in expression of osteonectin mRNA but prevented any further increase when Dex was added to retinoic acid-treated cells. To study transcriptional control, osteonectin genomic fragments were linked to the bacterial reporter gene, chloramphenicol acetyltransferase, and introduced by transfection into UMR 201 cells. Dexamethasone increased the transcriptional activity of an osteonectin-chloramphenicol acetyltransferase construct; 100 nM Dex resulted in a 3-fold increase over control cells which was attenuated when 1 microM retinoic acid was added to the incubation, while retinoic acid alone resulted in a 2-fold increase in transcriptional activity. Finally, it was noted that coincubation with retinoic acid and Dex stimulated the proliferation of UMR 201 cells when compared with either treatment alone. This study shows the potential importance of hormonal interactions in the expression of osteoblast function.
Mol Endocrinol 1989 Dec
PMID:Opposing influences of glucocorticoid and retinoic acid on transcriptional control in preosteoblasts. 262 42

In two cellular models of insulin resistance we measured glucose transport activity, total glucose transporter number using the cytochalasin B binding assay, and expression of a transporter mRNA species specifically hybridizing with cDNA cloned from brain. In primary cultured adipocytes, chronic exposure to glucose plus insulin (24 h), but neither agent alone, markedly decreased (less than 50%) glucose transport activity; however, neither glucose nor insulin regulated the number of glucose transporters or levels of transporter mRNA whether normalized per total RNA, RNA per cell, or as a fraction of CHO-B mRNA. On the other hand, chronic treatment with 30 nM dexamethasone (24 h) decreased basal and maximal transport rates (approximately 75%), led to a 40% depletion in total cellular glucose transporters, and decreased transporter mRNA by 57-59% (t 1/2 = 10 h; ED50 = 4-5 nm). Dexamethasone's effects to decrease transport rates, transporter protein, and mRNA were inhibited by coincubation with insulin. Dexamethasone did not alter the degradation rate of transporter mRNA relative to that in control cells indicating a lack of effect on mRNA stability. Also, suppression of transporter mRNA did not appear to require ongoing protein synthesis since the effect was observed when dexamethasone was added to cycloheximide-treated cells; however, cycloheximide per se specifically increased transporter mRNA 4-fold. We conclude in adipocytes: 1) glucose and insulin (24 h) do not regulate the total number of glucose transporters or expression of mRNA encoding a transporter species cloned from brain. 2) Long-term dexamethasone treatment reduces the cellular abundance of both glucose transporters and the specific transporter mRNA; these effects may be due to inhibition of gene transcription since dexamethasone does not influence transporter mRNA stability. 3) Insulin heterologously inhibits regulation of the glucose transport system by dexamethasone. 4) Dexamethasone-mediated insulin resistance is due in part to regulation of a glucose transporter species encoded by cDNA cloned from brain. These observations may be relevant to mechanisms of insulin resistance in clinical states of hypercortisolism.
Mol Endocrinol 1989 Jul
PMID:Expression of a glucose transporter gene cloned from brain in cellular models of insulin resistance: dexamethasone decreases transporter mRNA in primary cultured adipocytes. 267 80

Differential hybridization of a cDNA library from rat C6 glioma cells with cDNA probes from naive C6 glioma cells and from cells exposed to 17 beta-estradiol identified cDNAs of an mRNA stimulated by 17 beta-estradiol. This mRNA designated ESP1 mRNA, reached maximal levels after 8 h of treatment with 17 beta-estradiol. The stimulation was not suppressed by cycloheximide. Dexamethasone treatment of C6 glioma cells did not induce ESP1 mRNA. It codes for a 164 amino acids long peptide. The sequence is similar in part to that of CRIP protein, a probably member of the ferredoxin superfamily. The conservation of primary structure suggests a role of ESP1 peptide in oxygen consumption. ESP1 mRNA expression is sexually dimorphic in body tissue, whereas it is expressed to comparative levels in the brain of adult males and females. This suggests that 17 beta-estradiol stimulates the expression of the ESP1 gene in the brain of both gender.
Mol Cell Endocrinol 1989 Apr
PMID:Characterization of an estradiol-stimulated mRNA in the brain of adult male rats. 274 28

125I-Epidermal growth factor (EGF) binding capacity in fetal rat lung cells is decreased by approximately 50% following 24-h dexamethasone treatment. Ligand binding assays identified an average of 30,000 receptors per cell in untreated FRL cells, while analysis of dexamethasone treated cells showed a decrease to about 16,000 receptors per cell. No substantial changes in receptor affinities were detected. Immunoprecipitation of 35S-methionine-labeled EGF receptor protein demonstrated a 50% decrease in total EGF receptor protein after 24-h dexamethasone treatment. Brief pulse labeling with 35S-methionine showed that the reduction in total EGF receptor protein content was due to a decrease in EGF receptor synthesis. Receptor synthesis declined about 25% after 1 h of dexamethasone treatment and at 3 h, EGF receptor synthesis was maximally decreased to nearly 50% that of cells not exposed to dexamethasone. Dexamethasone treatment was also effective in reducing EGF receptor synthesis in cells pretreated with retinoic acid, an agent which enhances receptor synthesis. These data are the first to document a dexamethasone-induced decrease in EGF receptor synthesis. Furthermore, these findings may provide a plausible mechanism by which dexamethasone could regulate EGF responsiveness.
Mol Endocrinol 1989 Jun
PMID:Dexamethasone acts as a negative regulator of epidermal growth factor receptor synthesis in fetal rat lung cells. 278 89

The role of cytoplasmic activator of adenylate cyclase in rat lung metabolism was investigated. Mouse adrenal tumor (MAT) cells undergo differentiation in response to choleratoxin which acts through cyclic AMP. The activator of adenylate cyclase from rat lung also produced cyclic AMP in a disrupted MAT cell preparation. However, unlike choleratoxin, it did not induce MAT cell differentiation in whole cells. These results suggest impermeability of MAT cells, and possibly other cells, to the activator. Thus, means of altering activator activity in lung cytoplasm were sought, and changes in activator activity were related to lung glycogen. Adrenalectomy (ADX) in rats led to a reduction in activator activity that was accompanied by an elevation in lung glycogen. Dexamethasone treatment of adrenalectomized rats reversed both of these effects. Streptozotocin-induced diabetes in rats elevated activator activity and lowered lung glycogen. Insulin treatment of the diabetic rats restored activator activity to the normal control values. Preweaning of rats on day 16 instead of day 22 increased activator activity on the 19th day over the controls and there was a concomitant decrease in lung glycogen. Feeding the separated pups with homogenized milk restored glycogen and activator activity to the control values. These results indicate that activator activity in rat lung cytoplasm was dependent on the circulating levels of cortisol and insulin, and that there appeared to be an inverse relationship between activator activity and glycogen level in rat lungs.
Mol Cell Biochem 1988 Sep
PMID:Relationship between the cytoplasmic activator of adenylate cyclase and glycogen metabolism in rat lung. 285 15

Dexamethasone, a synthetic glucocorticoid, is required for full posttranslational maturation of mouse mammary tumor virus (MMTV) phosphoproteins and glycoproteins in M1.54 cells, a viral infected rat hepatoma (HTC) cell line. Pulse-chase radiolabeling with [35S]methionine revealed that steroids with known glucocorticoid activity (such as dexamethasone and hydrocortisone) regulated the maturation of both MMTV polyproteins in a manner proportional to their occupancy for glucocorticoid receptors and their biological potency. In contrast, progesterone selectively induced the proteolytic processing of MMTV phosphoproteins but simultaneously antagonized the dexamethasone-regulated maturation of MMTV glycoproteins and all other tested glucocorticoid responses. Exposure to suboptimal concentrations of both progesterone and dexamethasone fully stimulated the processing of MMTV phosphoproteins, suggesting that steroid receptors occupied with combinations of either steroid functionally interact at the putative maturation gene. Moreover, treatment with either actinomycin D, a potent inhibitor of de novo RNA synthesis, or RU38486, a synthetic antagonist of glucocorticoid and progesterone action, prevented both the dexamethasone and progesterone-regulated induction of MMTV phosphoprotein maturation. Sedimentation velocity and saturation binding analysis revealed that the sizes and concentrations of hepatoma cell progesterone and dexamethasone binding activities are similar while specific binding of the active progestin R5020 was not detected in either M1.54 cells or the glucocorticoid receptor deficient HTC cell line MSN6.10.2. Taken together, our results demonstrate that two distinct classes of steroid hormones can uniquely alter the posttranslational maturation of a specific subset of phosphoprotein substrates by a common glucocorticoid receptor-dependent process.
Mol Endocrinol 1987 Nov
PMID:Dual regulation of protein maturation in viral infected rat HTC hepatoma cells by glucocorticoids and progesterone. 285 2

Hepatocellular injury was induced by exposure of primary cultures of rat hepatocytes to 4 mM D-galactosamine. The cell damage was very similar to that seen in vivo and in the isolated perfused rat liver, both in biochemical and in structural terms. The severity of the lesions caused by D-galactosamine was dependent on the age of the culture being treated. Less severe damage was found with older cultures. Since the primary metabolic effects of D-galactosamine were age-independent, the reduction in cell damage seems to be due to progressive cell dedifferentiation. Dexamethasone (1 microM) suppressed the full development of the injury, while 1 microM triiodo-L-thyronine enhanced it. A protection of hepatocytes by alpha 2-macroglobulin against the effects of D-galactosamine could be observed neither in vivo nor in vitro. Direct cytotoxic effects of endotoxin from Salmonella minnesota R 595 could be demonstrated only on hepatocytes in the early phases of primary culture using rather high doses of the purified lipopolysaccharide. It is unlikely that they play a major role in the hepatocellular injury seen following endotoxinemia in vivo. Lowering of extracellular Ca2+ concentration and additions of calcium/calmodulin inhibitors did not prevent cell injury after treatment with D-galactosamine. The results suggest that cell death is not due to an increased influx of Ca2+ into the cells.
Exp Mol Pathol 1985 Feb
PMID:Toxicity of D-galactosamine for rat hepatocytes in monolayer culture. 285 29


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