Transcortin: A Corticosteroid-Binding Protein of Plasma. Iii. The Effects of Various Steroids *†

Abstract

In previous publications (1, 2) we have described some of the characteristics of transcortin, a plasma protein (or proteins) with high affinity for cortisol and corticosterone. In addition, we have shown that plasmiia transcortin levels are elevated during pregnancy and following administration of estrogens (1-3). A different interpretation of the findings in these two states has been given by Daughaday and AMariz (4,5). Transcortin levels were substantially lower in the plasma of newborn infants (umnbilical vein 1lood)1 than those found in adult subjects or in older children (2). The purpose of this paper is to present results of further studies on transcortin levels in human sub-*This investigation was supported in part by grants (A-1240-C3) 1lfl,17a,21-trihydroxy-pregnane-3,20-dione; tetrahydrocortisol (H4F) 3a,110,17a,21-tetrahydroxy-pregnane -20-one; 9a -fluorocortisol: 9a-fluoro-1 I,17a,21-trihydroxy-4-pregnene-3,20-dione; cortisone: 17a,21 -dihydroxy-4-pregnene-3,11,20-trione; di - jects under variotus condlitions and the effects of admiiniistered steroi(ls on these levels. MI ETHODS AND MATERIALSThe binding of C'4-cortisol by plasma transcortin and the transcortiin capacity were determined by methods previously described (1, 2). The terms "transcortin binding of C'4-cortisol" and "transcortin capacity" have been defiine(d in a previous publication (2). At this point it may be appropriate to reiterate some important aspects of the methodologies and terms used. Most of the binding experiments wvere performed by dialyzing 10 ml of diluted plasma (1: 5 with physiological saline) against 30 ml of saline containiing approximately 0.3 mg of C14-cortisol. The binding was (letermined with and without the addition of 1 ,ug of cortisol to the saline in order to measure the decrease in the binding caused by the addition of the carrier cortisol. In previously published work (1) we deimioinstrated that un(ler the con(ditions of our assay tlle bindinig of cortisol by plasma was essentially due to transcortini and not to other plasma proteins. Hence, the term "transcortiin bindiing of C'4-cortisol" will refer to the percentage of C'4-cortisol bound by 10 ml of diluted plasma and the term "transcortin capacity" will be used to in(licate the decrease in bindinig caused by the addition of 1 ,ug of cortisol in the dialysis conditions outlined above. It should be pointed out that the "binding capacity" will be inversely related to the decrease in the biniding caused by the addition of 1 ug of cortisol to normal plasma, i.e., the less the decrease in the binding the higher the binding capacity, and vice versa. The measurement of the binding capacity by the method outlined above seems to offer, at the moment, the most practical and sensitive index of traniscortin capacity. It should be realized, however, that this measures the difference between two variables, the level of transcortin and the level of 17-hydroxycorticosteroids (17-OHCS).Lymph was collected from the thoracic ducts of patients with advanced cancer in ice-ch...

Protein Binding of Corticoids Studied by Gel Filtration*

“…As suggested by others (22), no significant difference was found between normal males and females or between adults of different age groups (15 to 60 years). The low values noted in umbilical cord blood, and in certain patients with hypoalbuminemia and multiple myeloma, as well as the high ones induced by estrogen impregnation have also been reported already (20,22,24). As noted by Sandberg, Slaunwhite and Carter (24), the rise in cortisol-binding capacity induced by estrogen treatment precedes the elevation of unconjugated plasma corticoids.…”

“…According to the literature (20,24), saturation of transcortin with corticoids must occur at levels of 20 to 30 /Ag per 100 ml of plasma. The mean cortisol-binding capacity of 25.9 + 3.8 jug per 100 ml obtained with gel filtration is in line with this.…”

Inhibition by Estrogen Administration of Adrenal-Pituitary Response to Methopyrapone*

“…%4ETHOPYRAPO (14). This elevated level of plasma corticoids depends on an increased plasma level of transcortin (4,5). These elevated plasma 17-hydroxycorticoids were presumed to be biologically inactive because estrogen-treated patients presented none of the clinical features of Cushing's syndrome, because with these high plasma levels there was no increase in the glucosuria in diabetic patients (1), and finally, because, by the demonstration of Slaunwhite, Lockie, Back, and Sandberg (15), addition of transcortin to an ini vivo system blocks cortisone effect.…”

“…Each subject acted as his own control. Methopyrapone (2-methyl-1,2-bis-[3-pyridyl] -propanone) was given orally to these patients in doses of 500 or 750 mg every 4 hours for 2 days during the control period. The same doses were repeated during EE administration.…”

“…The glucosuric effect of exogenous hydrocortisone was much greater when ethinyl estradiol (EE) was administered together with the steroid, while a potentiating effect was not clearly demonstrated with a number of 1,2-unsaturated steroids. Estrogen therapy has been shown to increase the plasma levels of 17-hydroxycorticoids (2,3) owing to an increase in the levels of transcortin (CBG, corticosteroid-binding globulin) (4,5), but such a change does not occur in urinary corticoids, which may show a decrease (6).…”