Inhibition of cortisol production in isolated guinea-pig adrenal cells

Abstract

Cortisol, added to 1 ml incubation medium containing 3–4 × 10 5 isolated guinea-pig adrenal cells, provoked a decrease in basal and ACTH (250 pg)-stimulated cortisol production, in correlation with the amounts used (50 ng–2,000 ng). A decrease in aldosterone production could be seen when cortisol concentrations reached or exceeded 1,000ng/ml. There were no variations in either androgens (Δ 4-androstenedione, dehydroepiandrosterone) or 17-hydroxyprogesterone. Only 11-deoxycortisol was slightly increased. Using increasing concentrations of ACTH (50–250 pg), both in the absence and in the presence of 1,000ng cortisol, it was noted that the inhibition induced by cortisol was of a competitive type and could be overcome by ACTH. This decrease in cortisol was concomitant with an increase in 11-deoxycortisol. Neither corticosterone nor dexamethasone reduced cortisol production. In addition, it was shown that the conversion of tritiated 11-deoxycortisol to radioactive cortisol increased significantly under the influence of 250 pg ACTH (mean relative variation of 21.7% ± 7.7 (SEM), n = 6, P < 0.05); but decreased significantly under the combined effect of 1.000ng exogenous cortisol and the same dose of ACTH: (mean relative variation of 4.3% ± 1 (SEM), n = 8, P < 0.005). There is therefore reason to believe that the concentrations of cortisol at the adrenal level modulate the stimulation induced by ACTH and that this self-adjustment forms part of the control mechanisms involved in corticosteroidogenesis.