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At least 793 records · Page 44Linked to original sources
PubMed1993

Serum corticosteroid-binding globulin levels in children undergoing heart surgery.

Serum corticosteroid-binding globulin (CBG) levels were measured in children (mean age 4 years) during heart surgery. Considerable decrease in CBG level occurred between baseline examination (416 +/- 39 nM) and the day of surgery (314 +/- 30 nM). Relatively simple closed heart surgery did not influence CBG level with maximal cortisol level being 20 +/- 4 micrograms/dl. Open heart surgery under conditions of profound hypothermia (26 C, without extracorporeal circulation) caused dramatic lowering of CBG level, particularly striking after resuscitation (180 +/- 20 nM). At the same time cortisol level reached extremely high values (78 +/- 8 micrograms/dl). These data suggest that CBG is likely to play an important role in pituitary-adrenal response to surgery under severe conditions of hypothermia and cardiac arrest.

Cardiac Surgical Procedures↗
PubMed1994

In vivo effect of free fatty acids on the specific binding of glucocorticosteroids to corticosteroid binding globulin and liver receptors in immature rats.

Stimulating lipase activity with heparin (200 IU/kg b.w.) increased the plasma free fatty acid (FFA) concentration of immature rats (15 days). The effect of this elevated FFA concentration on glucocorticoid binding to corticosteroid binding globulin (CBG), and liver cytosol glucocorticoid receptor (GR), was analyzed. The plasma FFA concentration increased 2-fold, 10 minutes (P < 0.001), 20 minutes (P < 0.01), and 60 minutes (P < 0.01) post-heparin. The corticosterone (B) and progesterone concentrations were unchanged 60 minutes post-injection. The binding activity of immature rat CBG for B dropped 50% (P < 0.001) 60 minutes post-heparin injection, decreased B binding and increased plasma FFA were correlated (r = -0.8). The decreased B binding resulted from a 2-fold decrease in the apparent number of CBG binding sites; the affinity constant (Ka) remained unchanged. The liver cytosol endogenous FFA content of immature rats was also increased 2-fold, 60 minutes after heparin-induced lipolysis. The increased cytosol FFA, with no significant change in glucocorticoid, was accompanied by a significant decrease in dexamethasone binding to liver cytosol glucocorticoid receptor. The decrease resulted from a significantly lower apparent Ka for dexamethasone and fewer receptor binding sites (n). There was a good inverse correlation between Ka (r = -0.93) and n (r = -0.90) and the increased liver cytosol FFA content. Thus the higher plasma FFA induced in vivo by lipase activation or a standard FFA mixture probably causes conformational changes in CBG and GR, reducing glucocorticoid binding to immature rat CBG and liver GR.

Animals↗
PubMed1995

Expression of corticosteroid-binding globulin mRNA in human uterine endometrial cancers.

Since it has been demonstrated that corticosteroid-binding globulin (CBG) plays a role in intracellar steroidal actions in target cells, the expression of CBG mRNA as the measure of CBG expression was investigated in human endometrial cancers in order to assess the biological implications of CBG. The level of CBG mRNA was analyzed using competitive reverse transcription-polymerase chain reaction-Southern blot analysis. While the level of CBG mRNA was significantly (P < 0.01) higher in secretory phase endometrium than in early and late proliferative phase endometrium, the level of CBG mRNA tended to decrease with advanced dedifferentiation of endometrial cancers as compared to normal endometrium. These results suggest that dedifferentiation of endometrial cancers induces a reduction in intracellular CBG synthesis.

Adult↗
PubMed1995

Studies on the role of glycosylation in the origin of the electrophoretic variants for rat corticosteroid-binding globulin.

The glycoprotein corticosteroid-binding globulin (CBG) migrates as doublet bands in PAGE and SDS-PAGE, and as numerous bands in isoelectric focusing (IEF). This study deals with the origin of this heterogeneity. Desialation of rat CBG with neuraminidase does not abolish the doublet in either PAGE or SDS-PAGE, indicating that the doublet does not arise as a result of differences in sialic acid residues. Treatment of the separated upper and lower variants of native CBG with N-glycosidase F (PNGase-F) shows a differential pattern of deglycosylation over time indicating either differences in the number, type, or location of sugars attached to each of the variants. Rate of deglycosylation is quicker and more extensive for the upper variant when compared to the lower variant. PNGase-F treatment of 1% SDS-denatured CBG does not abolish the CBG doublet seen in SDS-PAGE, indicating that there is variation in the protein moiety. Sugars could not be detected on PNGase-F treated CBG using either wheat germ aglutinin horse radish peroxidase conjugate, concavilin-A HRP conjugate, or the digoxigenin glycan detection system. While the results clearly show differences in glycosylation between the CBG variants, differences in the protein moiety may also occur to give rise to the heterogeneity seen in CBG. The latter is supported by the fact that desialated CBG migrates as two bands in IEF. Migration in IEF is based solely on charge, and since only sialic acid residues are charged in N-linked glycosylation, any heterogeneity seen for the desialated glycoprotein must reside within the protein moiety itself. The presence of O-glycosylation containing an N-acetylgalactosamine with a beta 1-3 linkage to galactose could not be demonstrated using O-glycosidase. N-terminal blockage could not account for the variation, as both the upper and lower variants were able to be sequenced resulting in identical sequences for the first 13 amino acids. The data presented supports the hypothesis that the differences in the sugar as well as the protein moiety are responsible for the heterogeneity seen for CBG.

Amidohydrolases↗
PubMed1996

Corticosteroid and immune responses to cardiac surgery.

Serum corticosteroid-binding globulin (CBG) and cortisol levels as well as subsets of circulating immunocompetent cells (ICCs) were measured during cardiac surgery. Closed heart surgery (closed mitral commissurotomy) resulted in an elevation of cortisol levels (up to 32 +/- 5 micrograms/dL by the end of the surgery) with no changes in CBG and ICC levels observed. Open heart surgery (open reconstruction of the mitral valve) in surface-induced hypothermia (without extracorporeal bypass) caused a dramatic drop in CBG activity (from 250 +/- 17 microM before the beginning of anesthesia to 198 +/- 15 microM by the end of cooling (just before cardiac arrest) and 158 +/- 13 microM after 30 min of reperfusion), whereas cortisol levels were only slightly elevated by the end of cooling, and a significant increase (up to 17 +/- 2 micrograms/dL) was observed only at the end of the surgery (60 min of reperfusion and warming). Similar to CBG, a significant decline in circulating ICC contents occurred in response to cooling and circulatory arrest.

Adrenal Cortex Hormones↗
PubMed1989

Immunogenetic analysis of spontaneous autoimmune thyroiditis of obese strain chickens.

A variety of immunological, endocrinological, and virological abnormalities have been implicated in the etiopathogenesis of spontaneous autoimmune thyroiditis (SAT) of Obese strain (OS) chickens, e.g., a general T cell hyperreactivity, an increased uptake of iodine into the thyroid gland, a diminution of the glucocorticoid tonus, and an OS-specific endogenous virus. In crosses of the close-bred OS B15/B15 subline with the inbred normal CB B12/B12 strain we have studied the mode of inheritance of these aberrations and their putative association with SAT. The results indicate that none of these OS-specific characteristics alone is an absolute prerequisite for the development of thyroid infiltration, which appears to be governed by one autosomal recessive gene.

Animals↗
PubMed1994

Extreme posture elevates corticosterone in a forced ambulation model of chronic stress in rats.

The adrenocorticotropin (ACTH), corticosterone, and corticosterone-binding-globulin (CBG) levels in rats stressed chronically by a method designed to induce biomechanical stress were investigated in order to determine the relationship between degree of behavioral stress and evoked change in posture during forced ambulation and pituitary-adrenocortical hormone secretion. The method consists of forcing rats to ambulate and compares rats forced to ambulate in a normal (control group) and extreme (experimental) posture. In this method an extreme posture of relative extension was assumed by rats forced to ambulate inside a rotating cylinder. The numbers of faecal boli produced during forced ambulation were determined as a behavioral measure of stress. Rats forced to ambulate in cylinders produced more faecal boli while they ambulated than rats forced to ambulate on a flat surface. Rats forced to ambulate in cylinders had higher resting levels of corticosterone and lower levels of CBG than rats forced to ambulate on a flat surface. The higher corticosterone levels were not associated with increased ACTH levels. Because adaptation to forced ambulation resulted in higher corticosterone and lower CBG levels when exercise is performed in an extreme posture, it is suggested that extreme posture is stressful.

Adrenocorticotropic Hormone↗
PubMed1995

Differential activation of adrenal steroid receptors in neural and immune tissues of Sprague Dawley, Fischer 344, and Lewis rats.

Sprague Dawley (SD), Fischer 344 (F344), and Lewis (LEW) rats are used in a wide variety of laboratory studies. Compared to SD and LEW rats, F344 rats show significantly greater corticosterone secretion in response to stress, or to immune challenge. These strain differences in hypothalamic-pituitary-adrenal (HPA) axis responsivity have been the basis for many comparative studies investigating immunological and behavioural differences between the three strains. However, the effects of these strain differences in HPA axis responsivity have not been investigated at the level of adrenal steroid receptor activation in target tissues. The present study demonstrates that compared to SD and LEW rats, F344 rats exhibited a greater magnitude of Type II adrenal steroid receptor activation in brain tissues during stress. In contrast, Type II receptor activation in immune tissues of F344 rats following stress was similar to that of SD rats. Importantly, LEW rats exhibited the lowest magnitude of activation of Type II receptors in immune tissues during stress. No differences were observed between strains in the extent of stress-induced Type I adrenal steroid receptor activation. The observed differences between strains in corticosteroid-binding globulin (CBG) levels in plasma, pituitary, and immune tissue may mediate the differential access of corticosterone to neural versus immune tissues. These results indicate that strain differences in corticosterone secretion are manifested by differences in Type II receptor activation in neural as well as immune tissues. Moreover, they suggest that increased access of corticosterone to adrenal steroid receptors in brain areas of F344 rats may contribute to behavioural differences between strains, whereas decreased access of hormone to receptors in immune tissues of LEW rats may contribute to strain differences in susceptibility to autoimmune disease.

Adrenal Glands↗
PubMed1991

Positive cooperativity of [3H]dexamethasone binding to chick corticosteroid-binding globulin.

1. Dilution of chick plasma with Tris-EDTA buffer containing dithiothreitol (TED buffer) induced a positive cooperativity in the interaction between corticosteroids and CBG. 2. Positive cooperativity binding is probably induced by the polymerization of chick CBG in the presence of DTT. 3. As the increase of the value of B/F in Scatchard plot analysis was dependent on the concentration of [3H]dexamethasone, it is possible that the polymerization of CBG is steroid-dependent. 4. Positive cooperativity was also observed in TED buffer containing 0.2 M KCl and 0.5 M KCl. Addition of KCl seemed to enhance the polymerization of chick CBG.

Animals↗
PubMed1991

Protein binding of cortisol by means of competitive adsorption: application to cortisol binding by serum of sixteen eutherian mammals.

1. Binding of 3H-cortisol by serum proteins by means of competitive adsorption was relatively high by serum of the gerbil, human, rabbit, sheep, tree shrew, hamster, rhesus monkey and horse. 2. A somewhat lower binding was observed by serum proteins of the baboon, cattle, dog, rat and cat. 3. Serum taken from either the mouse, guinea pig or pig gave very flat binding curves, specific binding not exceeding 5% of added 3H-cortisol. 4. It is concluded that the measurement of protein-binding of 3H-cortisol by means of competitive adsorption is a reliable method for serum of most eutherian species but is unsuited if serum of the mouse, guinea pig or pig is used.

Adrenal Cortex Hormones↗
PubMed1987

Purification and partial characterization of a corticosteroid-binding globulin from hamster serum.

Our objective was to characterize and purify the corticosteroid-binding proteins in hamster pregnancy serum. When [3H]cortisol-labeled pregnancy and proestrous serum were subjected to native polyacrylamide gel electrophoresis, a single peak of specific steroid-binding activity was detected in each, with identical electrophoretic mobility. The steroid-binding affinity (Ka = 1.07.10(8) M-1 for cortisol) is typical of corticosteroid-binding globulin from other species, but the steroid-binding specificity (cortisol greater than testosterone greater than progesterone) is not. An ultraviolet photoaffinity-labeling protocol was developed using 17 beta-hydroxy-4,6-[1,2-3H]androstadiene-3-one ([3H]androstadienolone), permitting analysis of ultraviolet photoaffinity-labeled proestrous and pregnancy serum by two-dimensional polyacrylamide gel electrophoresis and fluorography. Both sera contained the same labeled protein species. Corticosteroid-binding globulin was purified from pregnancy serum by DEAE-cellulose chromatography followed by steroid affinity chromatography on androstadienolone-17 beta-hemisuccinate-ethylenediamine-AffiGel 10. The purified protein (Mr = 62,250; pI = 3.95; n = 1; Stokes radius = 3.5; S = 4-5) was determined to be a glycoprotein. When analyzed by gel filtration and two-dimensional polyacrylamide gel electrophoresis, purified corticosteroid-binding globulin behaved the same as in unfractionated serum, and when ultraviolet photoaffinity-labeled with [3H]androstadienolone, purified corticosteroid-binding globulin produced the same fluorogram spot pattern seen in unfractionated serum. A specific corticosteroid-binding globulin antiserum was raised in rabbits, and this antiserum reacted with a single spot in Western blots of unfractionated serum. Thus, hamster pregnancy serum was determined to have one corticosteroid-binding protein. This protein is identical to the corticosteroid-binding globulin found in proestrous serum, with a higher titer in pregnancy serum. No other steroid-binding component is observed in hamster serum.

Animals↗
PubMed1987

Feedback action and tonic influence of corticosteroids on brain function: a concept arising from the heterogeneity of brain receptor systems.

Two types of corticosteroid receptors can be distinguished in rat brain. The type 1 receptor resembles the kidney mineralocorticoid receptor and has two functional expressions in brain, i.e. type 1 corticosterone (CORT) preferring sites (CR) and mineralocorticoid receptors (MR). The type 2 receptor is similar to the liver glucocorticoid receptor (GR). CORT binds to both CR and GR. The localization, binding specificity, and capacity of the receptor systems have served as criteria to evaluate steroid dependent events in brain biochemistry and behaviour. The GR is widely distributed in neurons and glial cells, with the highest density in frontal brain regions. The GR becomes occupied concomitant with rising plasma CORT levels after stress and as part of the circadian rhythm. The GR mediates the feedback action of CORT on stress-activated brain processes. The CR has its predominant localization in neurons of the septo-hippocampal complex and has a ten-fold higher affinity for CORT than that of the GR. The CR is, at all times of intact adrenocortical secretion, 90% or more occupied by endogenous hormone. The CR mediates a tonic influence exerted with stringent specificity by CORT on hippocampus-associated functions, e.g. cognition, mood, and affect. CORT, via the CR, thus contributes to hippocampus function in interpretation of sensory information, leading to appropriate neuroendocrine and behavioural responses, which are themselves subsequently subject to feedback action via the GR. The MR mediates the mineralocorticoid effect on salt and water balance and its behavioural corollary of salt appetite. The anatomical localization of the MR system is as yet ill-defined, although functional studies suggest circumventricular organs as mineralocorticoid target sites. The CR and the MR have in common the high affinity for mineralocorticoids, but the CR is defined by its exclusive responsiveness to CORT as its agonist. The CR and MR probably represent the same chemical receptor modality (type 1), which is expressed differentially depending on the presence of extravascular corticosteroid binding globulin (CBG) in the vicinity of the receptor. GR capacity is subject to autoregulation. Chronic stress, senescence, and chronic CORT administration reduce GR number, with, as a consequence, a less efficient feedback signal. The CR number seems not to be under the control of corticosteroids, probably since the receptor sites are extensively occupied by endogenous hormones. The CR number displays a circadian rhythm and is reduced during senescence.(ABSTRACT TRUNCATED AT 400 WORDS)

Adrenal Cortex Hormones↗