Enhancement of the ACTH response to human CRH by pretreatment with the antiglucocorticoid RU-486.

The response of ACTH to an i.v. bolus injection of 100 micrograms human CRH at 09.00 h was investigated in five healthy men with and without pretreatment with the antiglucocorticoid RU-486 100 mg given orally 7 h before the injection of CRH. In all five subjects the plasma cortisol level immediately before CRH administration at 09.00 h was significantly higher after pretreatment with the antiglucocorticoid (17.1 vs 11.1 micrograms/100 ml). Despite this higher baseline cortisol level, in all subjects the maximal CRH-induced ACTH increase was more pronounced after RU-486 loading (delta max ACTH 39 vs 26 pg/ml). This observation proves that in man physiological concentrations of cortisol determine the response of the pituitary to CRH. Furthermore, the findings suggest reduced circulating glucocorticoid activity after administration of 100 mg RU-486, not completely compensated by an increase in plasma cortisol.