EFFECTS OF STEROID HORMONES ON PHYTOHEMAGGLUTININ-STIMULATED HUMAN PERIPHERAL BLOOD LYMPHOCYTES

Abstract

The interactions of steroid hormones and human peripheral blood lymphocytes (PBL) were investigated following glass-wool column separation of PBL and incubation in a serum-free medium in the presence of phytohemagglutinin (PHA). Addition of hydrocortisone or progesterone above physiological concentrations resulted in inhibition of [14C]2-TdR incorporation. 17.beta.-Estradiol and 5.alpha.-dihydrotestosterone inhibited [14C]2-TdR incorporation at steroid concentrations thousands of times higher than the physiological concentrations. The kinetics of hydrocortisone and progesterone inhibition was similar and suggested that events occurring early after PHA addition were most sensitive to steroid inhibition and that addition of steroid at 28 h, at the end of the early prereplicative phase of the cell cycle, inhibited DNA synthesis at very high concentrations. The PHA-induced increase in RNA synthesis was prevented by hydrocortisone addition even if delayed fro up to 4 h. Morphological transformation was similarly affected. The data, and other investigations showing that progesterone binds to a specific glucocorticoid receptor in PBL, suggest that the progesterone inhibition of macromolecular synthesis in human PBL is exerted via a glucocorticoid-like mechanism, and that glucocorticoid sensitivity is greatest during the early phases of lymphocyte activation. A rationale for the apparent in vivo immunosuppressive capability of progesterone was also provided.