Corticosterone binding

FI 1. Fleshner, M Deak, T Spencer, R. L Laudenslager, M. L., Watkins, L. R., and Maier, S. F A long term increase in basal levels of corticosterone and a decrease in corticosterone-binding globulin after acute stressor exposure. Endocrinology 136,5336-5342 (1995). 

Cell specificity of mineralocorticoid action is achieved in a different manner. Aldosterone, cortisol, and corticosterone bind with similar affinities to mineralocorticoid and glucocorticoid receptors. However, aldosterone activates only its own receptor in target tissues such as the kidney because of an enzyme, 110-hydroxysteroid dehydrogenase, that converts the prevalent glucocorticoids into inactive 11-keto derivatives but does not affect aldosterone. 

In animal studies, Cassano and D mello found that stress-induced activation of the HPA axis stimulated the release of both facilitatory and inhibitory components [109]. Stress can alter plasma corticosterone-binding globulin levels, and aminoglutethimide administration can cause accumulation of the corticosterone biosynthetic precursor, adrenal cholesterol. Their results indicated that stress-induced facilitation of the HPA axis is associated with the release of serotonin [109]. Djordjevic et al. also investigated the reaction of the HPA system to various stressors (fasting, crowding, cold, and heat) by... 

Corticosterone, the principal adrenosteroid, is a so-called stress response hormone and is bound to corticosterone-binding globulin in plasma. As shown in Fig. 11 [56], the plasma concentration of corticosterone in both AL and CR rats shows a similar diurnal variation, with the level increasing in... 

Ottenweller, J. E., A. H. Meier, A. C. Russo, and M. E. Frenzke. 1979. Circadian rhythms of plasma corticosterone binding activity in the rat and mouse. Acta Endocrinoligica (Copenhagen) 91 150-157. 

Angiotensin II binds to specific adrenal cortex glomerulosa cell receptors. The hormone-receptor interaction does not activate adenylyl cyclase, and cAMP does not appear to mediate the action of this hormone. The actions of angiotensin II, which are to stimulate the conversion of cholesterol to pregnenolone and of corticosterone to 18-hydroxycorticosterone and aldosterone, may involve changes in the concentration of intracellular calcium and of phospholipid metabolites by mechanisms similar to those described in Chapter 43. 

DeKloet, E., Wallach, G. and McEwen, B. Differences in corticosterone and dexamethasone binding in rat brain and pituitary. Endocrinology 96 598-609,1975. 

Pauly JR, Stitzel JA, Marks MJ, Collins AC (1989) An autoradiographic analysis of cholinergic receptors in mouse brain. Brain Res BuU 22 453 59 Pauly JR, Grun EU, Collins AC (1990a) Chronic corticosterone administration modulates nicotine sensitivity and brain nicotinic receptor binding in C3H mice. Psychopharmacology 101 310-316... 

GC exert their regulatory effects on the HPA system via two types of corticosteroid receptors the glucocorticoid receptor (GR) and the mineralocorticoid receptor (MR) (Reul and De Kloet 1985). GRs occur everywhere in the brain but are most abundant in hypothalamic CRH neurons and pituitary corticotropes. MRs, in contrast, are highly expressed in the hippocampus and, at lower expression levels, in hypothalamic sites involved in the regulation of salt appetite and autonomic outflow. The MR binds GC with a tenfold higher affinity than does the GR (Reul and De Kloet 1985). These findings on corticosteroid receptor diversity led to the working hypothesis that the tonic influences of corticosterone... 

Further radiolabeled ligand-binding assays have been reported for a wide variety of analytes, namely morphine and leu-enkephaline [30], (S )-propanolol [33], atra-zine [47], 17-jS-estradiol [59], 2,4-dichlorophenoxyacetic acid (2,4-D) [32], yohimbine and corynanthine [60], and corticosterone/cortisol [29]. Other assays are summarized in Table 3. 

Cortisol, corticosterone, aldosterone, and the synthetic steroids used in steroid therapy (e.g., prednisolone, dexamethasone, and triamcinolone) are glucocorticoid agonists and therefore elicit glucocorticoid responses. A number of other steroids bind to the glucocorticoid receptor and thus suppress glucocorticoid responses. 

Once the various steroids have been formed in paticular subcellular compartments, they must be released into the peripheral blood circulation. There is evidence that some steroids are released by passive diffusion, as in the case of corticosterone, but for 18-hydroxylated corticosteroids, Na+/K+-ATPase activity is necessary [6,109]. The situation is more complicated, however, because the presence of proteins in the adrenal cortex, which act as non-classical receptors, may bind C2i steroids to different extents, thus reducing rates of steroid release (see Ref. 6). So far as pregnenolone is concerned, there is no barrier to its efflux from the mitochondria where it is formed from cholesterol [50], During incubation of rat testis [110], pregnenolone was found to travel from the mitochondria, through the ER and cytosol and then out into the medium. The release with time could be resolved into two components, one rapid and the second, much slower. More than 25% of the pregnenolone remained in the tissue after 150 min. incubation. This two-phase release may reflect the presence of two pools of steroid, the initial loss representing passive dif-... 

Figure 16.16 Scatchard plot representing the interaction between cortisol and corticosterone with their receptor in hepatoma cell cytosol. (Reproduced by permission from Rousseau GG, Baxter JD, Tomkins GM. Glucocorticoid receptors relations between steroid binding and biological effects. J Mol Biol 67 99-115,1972.)...

In most studies, the selectivities of the MIPs have been estimated by measuring the amount of each ligand required to displace 50% of the binding of radiolabelled imprint species to the MIP (IC50). The first MIA study reported excellent selectivity of the theophylline method for theophylline (1,3-dimethylxanthine) in the presence of the structurally related compound caffeine (1,3,7-trimethylxanthine) [3]. Despite their close resemblance (they differ by only one methyl group), caffeine showed less than 1 % cross-reactivity. A similar level of specificity was recorded for cortisol and corticosterone MIPs, which were able to detect the absence and presence of single hydroxyl groups and double bonds in the steroid structure [13]. 

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