The Effect of Cortisol, Progesterone, and Transcortin on Phytohemagglutinin-Stimulated Human Blood Mononuclear Cells and Their Interplay

Abstract

The effect of transcortin on [3H]thymidine incorporation into phytohemagglutinin-stimulated human peripheral blood mononuclear cells and its influence on the well known suppressive effect of cortisol were investigated. Human transcortin by itself had no effect on thymidine incorporation between the concentrations of 0.25-1 X 10(-6) M. When transcortin was added to cortisol, the suppressive effect of cortisol decreased in proportion to the decrease in the protein-unbound cortisol concentration. We also investigated the influence of progesterone on transcortin-bound cortisol. When 0.5 and 1 X 10(-6) M transcortin, which contained 1 and 2 X 10(-7) M cortisol as a transcortin-bound form, were added to 5 X 10(-6) M progesterone, greater suppression of thymidine incorporation was observed that than produced by progesterone alone (86.1% and 81.3 for 0.5 and 1 X 10(-6) M transcortin, respectively). Moreover, when 5 X 10(-7) M transcortin containing the same amount of cortisol was added with 1, 2, and 5 X 10(-6) M progesterone, a greater suppression (92.6%, 74.1%, and 32.4% of control for 1, 2, and 5 x 10(-6) M progesterone) was demonstrated than that caused by progesterone alone (95.1%, 75.8%, and 49.5% of control for the corresponding concentrations of progesterone). This increased suppression was accompanied by an increase in the percentage of protein-unbound cortisol. These results indicate that unbound cortisol, whose concentration increases in the presence of progesterone, may be biologically active. The interaction between progesterone and cortisol may be modulated in part by the transcortin concentration.

Effect of β-endorphin and Cortisol on the PHA Stimulated Lymphoblastogenesis

“…It is well known that cortisol suppresses the lymphoblastogenesis in vitro. 24 – 28) In our results, cortisol suppressed the PHA stimulated lymphoblastogenesis in a dose dependent manner. It agrees with other reports and suggests that our experimental method used in the evaluation of suppressive effect of β-endorphin was not wrong.…”

Assessment of serum‐free cortisol levels in patients with adrenocortical carcinoma treated with mitotane: a pilot study

“…Eleven patients had plasma ACTH (2AE73 ± 0AE71 pmol/l, range: 1AE11-8AE22) and mitotane levels (16AE6 ± 0AE52 mg/l, range: [14][15][16][17][18][19][20] in the target range, and they also had FC (62AE10 ± 19AE91, P = 0AE24) Total studied samples r-= 0·78, P < 0·001 r-= 0·80, P < 0·001 r-= 0·70, P < 0·03 r-= 0·90, P < 0·001 r-= 0·58, P < 0·008 r-= 0·97, P < 0·001 r-= 0·58, P < 0·004 r-= 0·97, P < 0·001 The correlations between free cortisol levels and free cortisol index in the total samples studied, and in samples from patients of the different subgroups studied.…”

“…Cortisol circulates in blood largely bound to CBG and albumin, 17 with the much smaller amount of unbound hormone responsible for its metabolic effects. 15,18,19 It is assumed that the biologically active level of cortisol to which tissues are exposed is free cortisol (FC). Routinely available assays of adrenal function measure serum TC, but not the biologically active FC; it is usually considered that TC broadly correlates with the biologically-free fraction.…”

Possible new mechanism of cortisol action in female reproductive organs: physiological implications of the free hormone hypothesis

“…The free hormone hypothesis predicts that the biological activity of cortisol is proportional to the concentration of free hormone and not to the total concentration including the protein-bound fraction. Although this hypothesis may not be valid for all steroid hormones in every organ, there seems to be good evidence to suggest that it accounts for cortisol action in most situations (for review see Orth & Kovacs 1998) as supported by the following studies: (1) A reduced in vivo activity of CBPbound cortisol (Slaunwhite et al 1962), (2) a reduced suppressive effect of cortisol on mononuclear cell DNA synthesis in vitro in the presence of CBP (Ogawa et al 1983), (3) cortisol bound to CBP avoids metabolic degradation (Bright 1995), (4) the mechanism that regulates cortisol production correlates with the free rather than the total concentration and (5) the concentration of free cortisol in the circulation is usually normal in the presence of abnormal CBP levels (Mendel 1989).…”