Disease relevance of Serpina6

• Microcell transfer of human chromosome 14 from fibroblasts to rat hepatoma cells results in activation of alpha1AT and CBG transcription and chromatin reorganization of the entire locus [1].
• Consistent with hyperactivity in the HPA axis, lesioned rats had increased adrenal weight, decreased thymus and body weights and decreased plasma transcortin concentrations [2].
• The results of thermal inactivation and ammonium sulfate fractionation show the granuloma HC-binding protein closely resembles corticosteroid-binding globulin (CBG) [3].
• It is possible that the transcortin-like protein associated with the desheathed ganglion may be intracellular, as other investigators have suggested similar intracellular presence of a transcortin-like protein in the liver, uterus, and pituitary [4].
• Seventy-two hours of dehydration induced a decrease in body weight and CRH mRNA levels in PVN of controls as well as of FR50 rats, but also led to a rise in plasma corticosterone and free corticosterone without changing CBG binding capacity [5].

Psychiatry related information on Serpina6

• Ice bathing and cold exposure did not influence CBG, and water deprivation elevated serum CBG [6].
• Because circadian fluctuations in plasma proteins, including corticosteroid binding globulin (CBG), may be directly related to changes in locomotor activity, it is suggested that the attenuation of circadian changes in CBA and TPP were due to disruption of the daily cycle of locomotor activity [7].

High impact information on Serpina6

• We now show that there are differences between progesterone receptors in brain and uterus, and possibly in the distribution of the serum progesterone-binding protein, corticosteroid-binding globulin (CBG), which may enter uterine but not brain cells [8].
• Naturally occurring corticosteroids may have their primary actions in vivo at brain and hypothalamic sites of feedback, whereas synthetic glucocorticoids that do not bind to transcortin may act primarily on corticotropes and regions of brain outside the blood-brain barrier [9].
• The variant cells failed to activate either alpha1AT or CBG transcription, and chromatin remodeling failed to occur [1].
• The anti-DNA polymerase alpha IgG and beta-lapachone failed to affect the binding of tritiated estradiol, progesterone, or 5 alpha-dihydrotestosterone to their receptors in appropriate rat target tissues or the binding of [1,2-3H]hydrocortisone to serum transcortin [10].
• This suggested that [3H] progesterone was bound largely to a macromolecule distinct from transcortin, which does not bind glucocorticoids containing 9alpha-fluoro groups [11].

Chemical compound and disease context of Serpina6

• The animals were killed and for each sex the gonadectomized animals were compared with the hypophysectomized-gonadectomized animals as far as their NADPH- and NADH-dependent 3alpha-hydroxy-steroid dehydrogenases (3alpha-HSD) in renal microsomes, transcortin levels in serum and five organ weights relative to total body weight were concerned [12].

Biological context of Serpina6

• Furthermore, the single cysteine in rat CBG corresponds to one of two cysteines in human CBG, and this may be significant because a cysteine is located in the human CBG steroid binding site [13].
• Rat corticosteroid binding globulin (CBG) cDNAs were isolated from a lambda gt11 liver cDNA library [13].
• These findings support the hypothesis that the CBG level is an interesting indicator for both insulin resistance and low grade inflammation [14].
• Corticosteroid-binding globulin (CBG), the main plasma protein transport for cortisol, has been shown to be negatively regulated by insulin and IL-6, at least in vitro, suggesting that insulin resistance and inflammation may both contribute to decreasing CBG levels [14].
• The amino acid substitution identified in BB rat CBG therefore clearly accounts for the reduction in its steroid binding affinity, and further analysis of this and other natural CBG variants may reveal important information about the CBG steroid binding site [15].

Anatomical context of Serpina6

• Nevertheless, because CBG has been shown to be expressed by the adipose tissue, decreased CBG could create locally increased cortisol disposal, with no change in circulating cortisol, and facilitate fat accumulation, insulin resistance, and type 2 diabetes [14].
• This developmental related change in the rate of synthesis of CBG by the fetal hepatocytes may regulate the level of free (active) glucocorticoid in the fetal circulation and thereby the initiation and regulation of glucocorticoid-dependent processes during the crucial stages of the differentiation of fetal liver and other developing tissues [16].
• DNA binds neither free glucocorticoids nor those complexed with transcortin or cytosol proteins different from the receptor [17].
• CBG, albumin, and AFP accounted for 6, 11, and 25% (in 13-day-old rat fetuses) and 5, 15, and 28% (15-day-old rat fetuses), respectively, of the total secreted proteins in the culture medium [16].
• Plasma concentrations of ACTH and CBG and thymus wet weights were related to the measured concentration of free ultrafilterable B in plasma [18].

Associations of Serpina6 with chemical compounds

• Molecular radii were determined from Ferguson plots and were used in conjunction with sedimentation coefficients determined by sucrose density gradient centrifugation to calculate the molecular weights of the CBG [19].
• In a subsample of 120 men and 68 women, fasting serum free cortisol (calculated as the ratio fasting cortisol/CBG) was significantly associated with WHR (r = 0.24; P = 0.001), systolic (r = 0.18; P = 0.01) and diastolic (r = 0.19; P = 0.007) blood pressures, and HOMA value (r = 0.20; P = 0.005), but not with BMI or age [14].
• Rat transcortin, glucocorticoid binder IB, and an estrogen-binding protein from rat liver were not adsorbed by immune IgG-Sepharose [20].
• The dissociation rate constants of BB CBG for cortisol (4.42 nM) and corticosterone (1.43 nM) are both about 50% higher than those associated with Wistar CBG, but no obvious difference in the steroid binding specificity of BB and Wistar CBGs was detected [15].
• Thyroxine, at physiologic concentrations, resulted in an increased secretion of TeBG but not CBG [21].
• Unlike thyroxin-bound thyroxin-binding globulin, the cortisol-bound CBG displays an "active" serpin conformation with the proteinase-sensitive, reactive center loop (RCL) fully expelled from the regulatory beta-sheet A [22].

Regulatory relationships of Serpina6

• It is concluded that changes in the secretion of glucocorticoids and prolactin are not required for the observed turpentine-induced decrease of transcortin and alpha 2u-globulin [23].

Other interactions of Serpina6

• Body weight (b.w.) gain, plasma transcortin and thymus weight were reduced to a greater extent by chronic corticosterone in BN rats than in F344 rats, possibly as a consequence of higher free, active fraction of plasma corticosterone due to lower plasma transcortin concentrations and/or a greater efficiency of GR-related mechanisms in BN rats [24].
• 11-ketoprogesterone exhibits 17 times better affinity for native type 1 mineralocorticoid receptor than HOP and a 3-fold affinity for partially purified (transcortin free) mineralocorticoid receptor [25].
• Transcortin and alpha 2u-globulin messenger RNA activities during turpentine-induced inflammation in the rat [26].

Analytical, diagnostic and therapeutic context of Serpina6

• In both sexes serum CBG levels were correlated negatively with age (r = -0.12; P = 0.04), body mass index (r = -0.31; P < 0.0001), waist to hip ratio (WHR; r = -0.39; P < 0.0001), systolic (r = -0.15; P < 0.01) and diastolic (r = -0.15; P = 0.01) blood pressures, and HOMA, an index of insulin resistance (r = -0.12; P = 0.04) [14].
• Time course of the effect of adrenalectomy on transcortin binding characteristics: appraisal of different methods of calculation [27].
• Because of the high level of homology, we were able to use a cRNA prepared from a rat CBG cDNA as a probe in Northern blot and solution hybridization analyses [28].
• Rat CBG was purified by affinity chromatography and its precise concentration was determined by amino acid analysis [29].
• Corticosteroid-binding globulin (CBG) levels were measured in serum samples collected sequentially from rats into which indwelling catheters had been inserted [30].

References