The Rate Constants for the Interaction of Cortisol and Transcortin, and the Rate of Dissociation of Transcortin-Bound Cortisol in the Liver

Paterson, J. Y. F.

doi:10.1677/joe.0.0560551

Cited by 18 publications

(6 citation statements)

References 17 publications

(34 reference statements)

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“…The high rate of exchange of cortisol between the two pools and the increase in cortisol MCR with increased plasma levels of cortisol are consistent with the low binding capacity found in the plasma of adult male guinea-pigs. This is in general agreement with the view that the strong association of corticosteroid with transcortin protects the steroid from the catabolism, although in normal conscious sheep, Paterson (1973) has shown that the total splanchnic uptake of cortisol was derived from unbound (42%), albumin-bound (31%) and transcortin-bound steroid (27%). The stress induced by immobilization and luminous stimulation significantly increases the mean transcortin-binding capacity for cortisol (5T).…”

Section: Discussionsupporting

confidence: 89%

Effects of Acute Neurotrophic Stress on Peripheral Metabolism of Cortisol in Conscious Male Guinea-Pigs

Manin¹,

Delost²

1981

Journal of Endocrinology

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Cortisol metabolism was studied in conscious adult male guinea-pigs subjected to a neurotrophic stress (immobilization and stimulation by light for 3 h). The disappearance curves of tracer quantities of [3H]cortisol were represented by a two-pool model. In stressed animals, there was marked increase in the mean plasma level of cortisol (184% of control value; P less than 0.001) and in the metabolic clearance rate (MCR; 17% of control value; 0.001 less than P less than 0.001). This rise in the MRC of plasma cortisol resulted from an increase in the mean total apparent volume of distribution (49%, P less than 0.001). The lack of significant differences in the slopes of the second exponential phase of the disappearance curves indicated that the stress did not significantly increase the half-lie of cortisol. The mean binding capacity of transcortin for cortisol (ST) was significantly higher in the animals which had been subjected to the neurotrophic stress than in the control guinea-pigs (0.02 less than P less than 0.05). However, ST values remained very low and accounted for the very high levels of free cortisol found after the stress. The results suggest that the raised concentrations of unbound cortisol found in the plasma of conscious adult male guinea-pigs in response to neurotrophic stress reflect a hypersecretion of corticosteroid.

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Section: Discussionsupporting

confidence: 89%

Effects of Acute Neurotrophic Stress on Peripheral Metabolism of Cortisol in Conscious Male Guinea-Pigs

Manin¹,

Delost²

1981

Journal of Endocrinology

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“…The kinetics of steroid dissociation from CBG have been reported from several laboratories. Only Rosner et al (1973) used purified CBG; Dixon (1968) and Paterson (1973) worked with whole plasma. All three studies entailed use of radiolabeled steroids and a method of physically separating bound from free steroid.…”

Section: Discussionmentioning

confidence: 99%

Kinetic and equilibrium studies on steroid interaction with human corticosteroid-binding globulin

Stroupe¹,

Harding²,

Forsthoefel³

et al. 1978

Biochemistry

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Kinetic and equilibrium studies on the interaction of steroids with human corticosteroid-binding globulin (CBG, transcortin) were performed with pH, temperature, and steroid structure as variables. Dissociation rate constants were determined fluorometrically; the values for cortisol, corticosterone, deoxycorticosterone, and progesterone are 0.031, 0.047, 0.10, and 0.16 s-1, respectively, at 20 degrees C, pH 7.4. The pH dependence of the dissociation rate constant for the corticosterone complex below pH 10.5 at 20 degrees C is given by koff = 0.043 (1 + [H+]/10(-6.50)) s-1; above pH 11, koff = 0.030 (1 + 10(-12.15/[H+] s-1. A temperature-dependence study of koff for the cortisol and progesterone complexes gave values of 0.0028 s-1 and 0.012 s-1 at 4 degrees C, respectively, and 0.88 s-1 and 4.5 s-1 at 37 degrees C, with progesterone dissociating about four to five times faster over the entire temperature range. The affinity constants, determined by equilibrium dialysis, for the binding of cortisol, corticosterone, and progesterone at 4 degrees C were 7.9, 7.2, and 7.0 X 10(8) M-1; values of 0.40 and 0.26 X 10(8) M-1 were determined at 37 degrees C for cortisol and progesterone. The close similarity of the affinity constants of the three steroids combined with differing dissociation rates implies that the association rate changes with steroid structure, in contrast to our earlier findings with progesterone-binding globulin.

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“…On the other hand, the presence of receptor sites for glucocorticoids on the cell membranes of certain tissues may well provide a mechanism whereby the entry of cortisol into specific target cells is facilitated (Sekeris & van der Meulen, 1974). Indeed, the work of Paterson (1973) in sheep indicates that the hepatic uptake of cortisol from plasma during its passage through the liver is derived 42% from unbound cortisol, 3 I", from albumin bound and 27O, from CBG-bound cortisol. Since CBG-bound cortisol is by far the largest fraction present in the plasma it therefore represents the greatest source of cortisol for hepatic uptake.…”

Section: Thyroid Diseasementioning

confidence: 99%

Human Corticosteroid Binding Globulin

Brien

1981

Clinical Endocrinology

181

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SUMMARY The literature on corticosteroid binding globulin (transcortin) in the human is reviewed under the following headings: physicochemical properties, biosynthesis, measurement, and physiological, pharmacological and pathological variations with particular emphasis of the effects of pregnancy and oral contraceptives. Finally, the physiological implications of corticosteroid binding globulin are discussed.

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The Rate Constants for the Interaction of Cortisol and Transcortin, and the Rate of Dissociation of Transcortin-Bound Cortisol in the Liver

Cited by 18 publications

References 17 publications

Effects of Acute Neurotrophic Stress on Peripheral Metabolism of Cortisol in Conscious Male Guinea-Pigs

Effects of Acute Neurotrophic Stress on Peripheral Metabolism of Cortisol in Conscious Male Guinea-Pigs

Kinetic and equilibrium studies on steroid interaction with human corticosteroid-binding globulin

Human Corticosteroid Binding Globulin

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