Disease relevance of SERPINA6

• We investigated the hypothesis that corticosteroid-binding globulin (CBG) polymorphism could influence obesity, metabolic, or hypothalamo-pituitary adrenal (HPA) axis activity parameters [1].
• Furthermore, these observations may be relevant to obesity occurring with suppressed CBG concentrations associated with hyperinsulinemia [2].
• These results suggest that dedifferentiation of endometrial cancers induces a reduction in intracellular CBG synthesis [3].
• A steroid binding capacity assay and a radioimmunoassay were both used to measure corticosteroid binding globulin (CBG) in serum samples from 22 patients with sepsis [4].
• Although relative hypotension and fatigue have recently been associated with CBG deficiency in a family with two CBG mutations (null and Lyon), the two homozygous subjects in this kindred were both normotensive and only the proband presented with fatigue [5].

Psychiatry related information on SERPINA6

• In addition, CBG was significantly increased in PTSD subjects, and DHEA was significantly decreased in both PTSD and combat-exposed control subjects [6].
• The binding capacity and apparent binding affinity of corticosteroid-binding globulin (CBG) for cortisol was studied in 20 women hospitalized for anorexia nervosa [7].
• We were interested in determining if acute food restriction (such as might occur during inclement weather) is a sufficient cue to elicit an increase in locomotor activity, increase CORT secretion, and/or decrease circulating levels of corticosterone binding globulin (CBG) in white-crowned sparrows (Zonotrichia leucophrys gambelii) [8].

High impact information on SERPINA6

• Identification of breast cancer transcortin and its inhibitory role in cell-mediated immunity [9].
• Comparisons between serum steroid binding capacities and immunoassayable SHBG and CBG concentrations did not reveal abnormal forms of either protein [10].
• Placental transcortin differs from plasma transcortin in that it has a smaller sedimentation coefficient (3S vs 3.75S) and binds cortisol less strongly [11].
• This purified protein is able to block the phytohemagglutinin response of maternal lymphocytes even more than serum transcortin [11].
• The syncytiotrophoblastic cells of the human placenta contain a cytoplasmic protein recognized by fluorescein-labeled transcortin-specific antibody [11].

Chemical compound and disease context of SERPINA6

• Also, GC from patients with endometriosis produced equal amounts of P4 and CBG than controls without the disease, either in freshly isolated cells or in 24-h cultures [12].
• PURPOSE: A high serum cortisol concentration, apparently due to increased cortisol-binding globulin (CBG), was found in a patient (index case) with chronic active hepatitis (CAH) [13].
• After oral prednisone or intravenous prednisolone, patients with hyperthyroidism had lower albumin-bound, transcortin-bound, and unbound concentrations of prednisolone but normal affinities of albumin and transcortin for prednisolone binding [14].
• The effects of ethinylestradiol (1 mug/kg body weight daily) on plasma renin substrate concentration, other factors of the renin-aldosterone-system, and on the cortisol-binding capacity of transcortin were determined in 8 young men and 9 young women [15].
• Assessment of 1600h plasma cortisol, ACTH and corticotrophin binding globulin (CBG) in response to dexamethasone in PTSD patients and trauma controls [16].

Biological context of SERPINA6

• In 44 obese pre-menopausal women, a microsatellite located within the CBG gene was analyzed, providing three genotypes: 86/86 (n = 29), 86/90 (n = 14), and 90/90 (n = 1) [1].
• The deduced amino acid sequence of mature CBG contains two cysteine residues and consensus sequences for the attachment of six possible N-linked oligosaccharide chains [17].
• The liver CBG cDNA contains an open reading frame for a 405-amino acid (Mr 45,149) polypeptide [17].
• A second, in-frame, 72-base-pair cistron of unknown significance exists between the TAA termination codon for CBG and a possible polyadenylylation signal (AATAAA) located 16 nucleotides before the polyadenylylation site [17].
• The sequences of the human lung and liver CBG cDNAs differ by only one nucleotide within the proposed leader sequence, and we attribute this to a point mutation [17].

Anatomical context of SERPINA6

• Our results indicate that CBG mRNA is relatively abundant in the liver but is also present in the lung, testis, and kidney [17].
• We sought information on the occurrence of CBG in the cytosol, nuclear, and membrane fractions of 6 tissues during decidualization in the hamster [18].
• Rodent studies suggest that corticosteroid-binding globulin (CBG) modulates glucocorticoid action in adipose tissue [2].
• Membrane CBG was highest in liver, 5-fold less in deciduoma, 10-fold less in myometrium, and about 20-fold less in other tissues [18].
• Nuclear CBG concentration was greatest in liver and approximately 10-fold less in other tissues, except for small intestine, where nuclear CBG was undetectable [18].

Associations of SERPINA6 with chemical compounds

• The antibodies did not crossreact with other rabbit steroid receptors (uterine estradiol receptor and liver glucocorticoid receptor) or with nonreceptor progesterone-binding proteins (transcortin from plasma and uteroglobin from uterine fluid) [19].
• This includes a predominantly hydrophobic, leader sequence of 22 residues that precedes the known NH2-terminal sequence of human CBG [17].
• A filter disk assay was developed both for the measurement of plasma corticosteroid-binding globulin (CBG) and for the cortisol-binding protein in milk [20].
• A detailed comparison of CBG derived from milk and plasma showed that the two proteins co-migrated on Sephadex, sucrose gradient ultracentrifugation, and polyacrylamide gel electrophoresis [20].
• In addition to low affinity, CBG from squirrel monkeys and other New World primates exhibits differences in electrophoretic mobility and sedimentation behavior in sucrose density ultracentrifugation, suggestive of a molecular weight that is approximately twice that of CBG from other species [21].
• The steroid binding properties of CBG variants with substitutions at P15 (G335P), P14 (V336R), or P12 (T338P) in the RCL hinge were largely unaffected after elastase cleavage, most likely because the re-orientation and/or insertion of the cleaved RCL was blocked [22].

Physical interactions of SERPINA6

• Glucocorticoid receptor number and binding characteristics and 11beta-hydroxysteroid dehydrogenase activity were similar for CBG-negative and normal preadipocytes [2].
• Recently, much evidence has indicated that sex hormone-binding globulin (SHBG) and corticosteroid-binding globulin (CBG) play a role in the intracellular action of sex steroids in target cells [23].

Other interactions of SERPINA6

• CBG-negative preadipocytes proliferated more rapidly and showed greater peroxisome proliferator-activated receptor-gamma-mediated differentiation than normal preadipocytes [2].
• Fractions containing SHBG or CBG were finally purified by liquid-liquid chromatography on Lipar-Gel 750 [24].
• The receptor is distinct from glucocorticoid receptor and CBG as determined by competition studies using dexamethasone and hydrocortisone [25].
• The genes encoding alpha 1-antitrypsin (alpha 1AT; gene symbol PI) and corticosteroid-binding globulin (CBG) are part of a cluster of structurally related serine protease inhibitor (serpin) genes on human Chromosome (Chr) 14q32 [26].
• Since progesterone itself binds to glucocorticoid receptor, to corticosteroid binding globulin (CBG), and to nonspecific components as well as to its own receptor, we have used a synthetic progestin, R5020 (17,21-dimethyl-19-nor-4,9-pregnadiene-3,20-dione), whose binding specificity is restricted to progesterone receptor [25].

Analytical, diagnostic and therapeutic context of SERPINA6

• The high levels of CBG in uterine tissues were not the result of serum contamination because whole-body perfusion with buffered saline failed to remove the majority of cytosol CBG under conditions where over 70% of 51Cr-labeled red blood cells were removed [18].
• The identity of uterine cytosol CBG with serum CBG was established by ion-exchange chromatography (O-(diethylaminoethyl)-cellulose) and by immunoprecipitation with an antibody generated against serum CBG [18].
• Cortisol and CBG levels in serum were measured by radioimmunoassay (RIA) [5].
• In the present work, CBG mRNA was detected in normal human endometrial tissues by Northern blot analysis and reverse transcription-polymerase chain reaction [27].
• In Western blot analysis, polyclonal anti-CBG antibodies recognized a protein of approximately 55 kD in the protein extracts prepared from 3A (tPA-30-1) cells [28].

References