Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P56851 (epididymal)
 11,273 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Monoclonal antibodies directed against four different polypeptide epitopes on the Mr approximately 94,000 steroid-binding subunit of the rat liver cytosolic glucocorticoid receptor (GcR) were used to probe Western blots of epididymal spermatozoa from rats and mice. Two sperm polypeptides with apparent molecular weights of 94,000 (indistinguishable in size from the liver GcR subunit) and 150,000 reacted with these antibodies. Other polypeptides that are present in a wide variety of somatic cells [lamin-A, -B, and -C; topoisomerase-I; poly(ADP-ribose) polymerase; the 62-kilodalton internal nuclear matrix protein; the nucleolar protein B23; and histone H1] could not be detected in these preparations of spermatozoa, thus appearing to rule out contamination by somatic cells. Rat and mouse pachytene spermatocytes and round spermatids contained much lower amounts of the Mr approximately 94,000 and 150,000 polypeptides. These results suggested that the steroid-binding subunit of the GcR might be accumulated late in spermatogenesis. Consistent with this view, a 6-kilobase mRNA (identical in size to a mRNA detected in mouse somatic cell lines) was detected when Northern blots of mouse round spermatid RNA were probed with a cDNA to the steroid-binding GcR subunit. Although the results described above suggest the presence of GcR in rodent sperm, high affinity binding of glucocorticoids to epididymal sperm could not be detected in a whole cell binding assay. Further analysis revealed that the Mr approximately 90,000 heat shock protein (hsp90), a component reportedly required for high affinity ligand binding to the GcR, was present in early germ cells, but absent from rodent epididymal sperm. These results suggest that the Mr approximately 94,000 steroid-binding subunit of the GcR and an immunologically related Mr approximately 150,000 polypeptide are specifically accumulated during the later stages of rodent spermatogenesis, but are not assembled into receptor complexes capable of binding steroid. In addition, these results support the view that hsp90 is required for high affinity binding of glucocorticoids to the Mr approximately 94,000 GcR subunit in intact cells.
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PMID:Evidence that rodent epididymal sperm contain the Mr approximately 94,000 glucocorticoid receptor but lack the Mr approximately 90,000 heat shock protein. 157 14

The nucleomyofibrillar fraction of epididymides from sexually mature rabbits contains a novel leupeptin-sensitive protease that disrupts the oligomeric conformation of cytosolic estrogen and progesterone receptors, and molybdate inhibits this process. In this report we used the AtT-20 cell glucocorticoid receptor as substrate and performed analyses under nondenaturing vs. denaturing conditions to further investigate the effects of the epididymal protease and molybdate on steroid receptor structure. Analysis on low salt sucrose gradients indicated that the protease partially converted the oligomeric (9-10S) glucocorticoid receptor to several more slowly sedimenting forms (3-7S), and this effect was not observed in the presence of molybdate. Paradoxically, gradient analysis under high salt conditions revealed that the protease induced a discrete, quantitative and molybdate-insensitive conversion of the 4-5S steroid-binding subunit to a 3S form. Further studies were done using denaturing polyacrylamide gel electrophoretic analysis of receptor that had been labeled covalently with [3H]dexamethasone 21-mesylate and partially purified by DNA/cellulose chromatography. At 0-4 C, the protease cleaved the steroid-binding subunit (mol wt, 96,900) of the receptor to a single steroid-labeled fragment (mol wt, 42,600). Under these conditions, digestion was complete within 30-60 min and was inhibited by leupeptin, but was unaffected by thiol-reactive reagents or molybdate. The epididymal protease and alpha-chymotrypsin produced steroid-labeled receptor fragments that were indistinguishable in size, shared an epitope recognized by our BuGR-2 monoclonal antibody, and retained DNA-binding activity. Despite the apparent similarity of these two enzymes, they are distinct, since the chymotrypsin-dependent cleavage event was not inhibited by leupeptin. These studies show that the epididymal protease attacks a site on the steroid-binding subunit of glucocorticoid receptors as well as estrogen and progestin receptors. It also appears that the cleavage site is situated close to that most readily attacked by alpha-chymotrypsin. Finally, our data provide independent confirmation of a recent report indicating that molybdate ions interact directly with the cytosolic steroid receptor to stabilize its oligomeric structure even after proteolysis within the steroid-binding subunit.
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PMID:Analysis of the disruptive action of an epididymal protease and the stabilizing influence of molybdate on nondenatured and denatured glucocorticoid receptor. 354 7

An affinity chromatography technique has been utilized to compare the rates of putative glucocorticoid receptor biosynthesis in epididymal fat pad adipocytes of mature and senescent Wistar rats. Biosynthetic rates appear to be linear for at least 3 hours in both age groups, but are reduced by about one-half in the senescent cells. In contrast, incorporation of labeled amino acids into total protein is not altered with aging in this system. Thus, reduction in putative glucocorticoid receptor biosynthetic rate may reflect the effects of senescence on the expression of only a small part of the genome.
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PMID:Biosynthetic rates of proteins having the characteristics of glucocorticoid receptors in adipocytes of mature and senescent rats. 725 67

Previous quantification of glucocorticoid receptor (GR) binding in adipose tissue has been performed in cytosol preparations, which did not allow the determination of the total number of GR in the cell. Therefore, GR binding was determined in intact adipocytes. Dexamethasone (dex) was used as a ligand in adipocytes isolated from epididymal (Epi), retroperitoneal (Ret), inguinal (Ing) and mesenteric (Mes) adipose tissue regions in male rats. The binding was saturable and specific with a Kd in the nanomolar range, not different from previously reported affinity of binding in cytosol preparations from adipocytes. Binding capacity rose after removal of endogenous glucocorticoids either by adrenalectomy (ADX) or culture in a glucocorticoid-free medium. Binding capacity of adipocytes was in general higher in Mes adipose cells than in adipocytes from Epi, Ing and Ret tissues from intact and ADX animals when expressed per unit of triglyceride weight of adipose tissues. This seemed to be largely explainable by a higher cellular density in Mes than in other adipose tissues. When comparisons were performed with binding per adipocyte, intraabdominal (Epi, Ret and Mes) cells bound more dex than adipocytes from subcutaneous (Ing) adipose tissue. It is suggested that in comparison with other adipose tissues Mes tissue has a higher density of the GR in situ, due mainly to a higher cellular density. Intraabdominal adipocytes in general seem to have a higher GR density than subcutaneous cells. This might explain the high activity of glucocorticoid-regulated metabolic pathways in intraabdominal particularly Mes adipose tissue.
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PMID:Glucocorticoid hormone binding to rat adipocytes. 794 39

Energy balance and lipid metabolism were investigated in transgenic mice bearing an antisense glucocorticoid receptor (GCR) gene construct that impairs the normal expression of the GCR gene. Food intake was recorded during the 15 days preceding decapitation of adult normal and transgenic mice, and feces were collected to derive the digestible energy intake. Body composition measurements consisted of the determination of energy, protein, and fat content of the carcass. Carcass energy was determined by bomb calorimetry, whereas carcass protein was measured by the Kjeldahl procedure. Energy expenditure was estimated from the continuous oxygen consumption (VO2) monitoring over a 24-h period. Lipoprotein lipase (LPL) activity was quantified in epididymal white adipose tissue (WAT), heart, and vastus lateralis muscle (VLM) by measuring the in vitro hydrolysis of labeled triolein in the presence of tissue homogenates. Norepinephrine (NE) content of both interscapular brown adipose tissue (BAT) and heart were determined by high-performance liquid chromatography (HPLC). Energy intake and expenditure were significantly lower in transgenic mice than in controls. Concurrently, both fat content and total energy of the carcasses were significantly higher in the transgenic animals. In comparison with normal mice, heart and VLM LPL activity was significantly reduced in transgenic mutants. There was no difference between groups in LPL activity in WAT. Finally, heart and BAT NE contents were lower in transgenic animals than in control mice. These results suggest that a defective GCR system may affect energy balance through increasing energetic efficiency, and they emphasize the modulatory effects of hypothalamic-pituitary-adrenal axis changes on muscle LPL activity.
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PMID:Energy balance and lipid metabolism in transgenic mice bearing an antisense GCR gene construct. 834 80

The relationship of leptin gene expression to adipocyte volume was investigated in lean 10-wk-old male C57BL/6J mice. mRNA levels for leptin, insulin receptor, glucocorticoid receptor, and tumor necrosis factor (TNF)-alpha in inguinal, epididymal, and retroperitoneal adipose tissues were quantified and related to adipocyte volume. Leptin mRNA levels were highly correlated with adipocyte volume within each fat depot. Multiple regression analysis of pooled data from the three depots showed that leptin mRNA levels were strongly correlated with adipocyte volumes (beta = 0.84, P < 0.001) and, to a smaller degree, with glucocorticoid receptor mRNA levels (beta = 0.36, P < 0.001). Depot of origin had no effect (P > 0.9). Rates of leptin secretion in vitro were strongly correlated with leptin mRNA levels (r = 0.89, P < 0.001). mRNA levels for TNF-alpha, insulin receptor, and glucocorticoid receptor showed no significant correlation with adipocyte volume. These results demonstrate that depot-specific differences in leptin gene expression are mainly related to the volumes of the constituent adipocytes. The strong correlation between leptin gene expression and adipocyte volume supports leptin's physiological role as a humoral signal of fat mass.
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PMID:Determinants of leptin gene expression in fat depots of lean mice. 1174 42

In utero overexposure to glucocorticoids may explain the association between low birth weight and subsequent development of the metabolic syndrome. We previously showed that prenatal dexamethasone (dex) exposure in the rat lowers birth weight and programs adult fasting and postprandial hyperglycemia, associated with increased hepatic gluconeogenesis driven by elevated liver glucocorticoid receptor (GR) expression. This study aimed to determine whether prenatal dex (100 microg/kg per day from embryonic d 15 to embryonic d 21) programs adult GR expression in skeletal muscle and/or adipose tissue and whether this contributes to altered peripheral glucose uptake or metabolism. In utero dex-exposed rats remained lighter until 6 months of age, despite some early catch-up growth. Adults had smaller epididymal fat pads, with a relative increase in muscle size. Although glycogen storage was reduced in quadriceps, 2-deoxyglucose uptake into extensor digitorum longus muscle was increased by 32% (P < 0.05), whereas uptake in other muscles and adipose beds was unaffected by prenatal dex. GR mRNA was not different in most muscles but selectively reduced in soleus (by 23%, P < 0.05). However, GR mRNA was markedly increased specifically in retroperitoneal fat (by 50%, P < 0.02). This was accompanied by a shift from peroxisomal proliferator-activated receptor gamma 1 to gamma 2 expression and a reduction in lipoprotein lipase mRNA (by 28%, P < 0.02). Adipose leptin, uncoupling protein-3 and resistin mRNAs, muscle GLUT-4, and circulating lipids were not affected by prenatal dex. These data suggest that hyperglycemia in 6-month-old rats exposed to dexamethasone in utero is not due to attenuated peripheral glucose disposal. However, increased GR and attenuated fatty acid uptake specifically in visceral adipose are consistent with insulin resistance in this crucial metabolic depot and could indirectly contribute to increased hepatic glucose output.
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PMID:Programming of rat muscle and fat metabolism by in utero overexposure to glucocorticoids. 1258 77

Adipocytes isolated from epididymal adipose tissue of foot-shock stressed rats are supersensitive to isoprenaline and subsensitive to norepinephrine. These alterations are probably mediated by a stress-induced increase in plasma corticosterone levels. We investigated whether foot-shock stress modifies the expression of glucocorticoid receptors (GRs) and beta-adrenergic protein receptors (beta-ARs) in epididymal adipose tissue from rats submitted to one daily foot-shock session on three consecutive days. This stress protocol caused decreases in GR, beta(1)-AR, and beta(3)-AR protein levels, but caused an increase in beta(2)-AR. These results confirm and support previous functional studies. The alterations in protein expression may be modulated by the high corticosterone levels that downregulate the glucocorticoid receptor.
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PMID:Glucocorticoid receptor and Beta-adrenoceptor expression in epididymal adipose tissue from stressed rats. 1524 Mar 86

In this study, epididymal adipose tissue from male annexin 1 (ANXA1)-null and wild-type control mice were used to explore the potential role of ANXA1 in adipocyte biology. ANXA1 was detected by Western blot analysis in wild-type tissue and localized predominantly to the stromal-vascular compartment. Epididymal fat pad mass was reduced by ANXA1 gene deletion, but adipocyte size was unchanged, suggesting that ANXA1 is required for the maintenance of adipocyte and/or preadipocyte cell number. Epididymal tissue from wild-type mice responded in vitro to noradrenaline and isoprenaline with increased glycerol release, reduced IL-6 release, and increased cAMP accumulation. Qualitatively similar but significantly attenuated responses to the catecholamines were observed in tissue from ANXA1-null mice, an effect that was not associated with changes in beta-adrenoceptor mRNA expression. Lipopolysaccharide (LPS) also stimulated lipolysis in vitro, but its effects were muted by ANXA1 gene deletion. By contrast, LPS failed to influence IL-6 release from wild-type tissue but stimulated the release of the cytokine from tissue from ANXA1-null mice. ANXA1 gene deletion did not affect glucocorticoid receptor expression or the ability of dexamethasone to suppress catecholamine-induced lipolysis. It did, however, augment IL-6 expression and modify the inhibitory effects of glucocorticoids on IL-6 release. Collectively, these studies suggest that ANXA1 supports aspects of adipose tissue mass and alters the sensitivity of epididymal adipose tissue to catecholamines, glucocorticoids, and LPS, thereby modulating lipolysis and IL-6 release.
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PMID:Gene deletion reveals roles for annexin A1 in the regulation of lipolysis and IL-6 release in epididymal adipose tissue. 1683 95

The link between intra-abdominal adiposity and type II diabetes has been known for decades, and adipose tissue macrophage (ATM)-associated inflammation has recently been linked to insulin resistance. However, the mechanisms associated with ATM recruitment remain ill defined. Herein, we describe in vitro chemotaxis studies, in which adipocyte conditioned medium was used to stimulate macrophage migration. We demonstrate that tumor necrosis factor alpha and free fatty acids, key inflammatory stimuli involved in obesity-associated autocrine/paracrine inflammatory signaling, stimulate adipocyte expression and secretion of macrophage chemoattractants. Pharmacological studies showed that peroxisome proliferator-activated receptor gamma agonists and glucocorticoids potently inhibit adipocyte- induced recruitment of macrophages. This latter effect was mediated by the glucocorticoid receptor, which led to decreased chemokine secretion and expression. In vivo results were quite comparable; treatment of high fat diet-fed mice with dexamethasone prevented ATM accumulation in epididymal fat. This decrease in ATM was most pronounced for the proinflammatory F4/80(+), CD11b(+), CD11c(+) M-1-like ATM subset. Overall, our results elucidate a beneficial function of peroxisome proliferator-activated receptor gamma activation and glucocorticoid receptor/glucocorticoids in adipose tissue and indicate that pharmacologic prevention of ATM accumulation could be beneficial.
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PMID:Glucocorticoids and thiazolidinediones interfere with adipocyte-mediated macrophage chemotaxis and recruitment. 1974 Jul 50


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