Dose-related effect of hydrocortisone treatment on the electrokinetic properties and mitogen responsiveness of mouse...

The electrophoretic mobility (EPM) and the ability to synthesize DNA in vitro either spontaneously or in response to concanavalin A (Con A) and phytohemagglutinin (PHA) were investigated on thymocytes from adult female Swiss/B mice which had received intraperitoneally, 2 days previously, various doses (10-750 mg/kg body weight) of hydrocortisone acetate (OHC). A first group of thymocytes, highly sensitive to OHC, rapidly decreased in proportion following administration of increasing doses of OHC (10-125 mg/kg body weight) and included the totality of low-EPM thymocytes (EPM less than 1.0 mum sec-1 V-1 cm) together with about 70% of the high-EPM thymocytes encountered in the normal thymus. The second group of thymocytes (4% of the initial cellularity), which resisted to OHC at 125 mg/kg body weight and was only reduced by half with doses of OHC 6-fold larger, was composed essentially of high-EPM cells. The mean EPM of both groups tended to increase with increasing doses of OHC which suggests that among these two groups thymocytes are all the more OHC-sensitive as they possess a low surface charge. Spontaneous DNA synthesis, measurable on the first 24 h of in vitro cultivation, markedly dropped after treatment with OHC at doses higher than or equal to 62 mg/kg body weight. This loss of early spontaneous proliferation coincided with the disappearance of medium-EPM thymocytes. By contrast, proliferative response of thymocytes to mitogens was enhanced by OHC pretreatment of donors and roughly paralleled the enrichment in high-EPM cells. However, administration of the largest amounts of OHC diminished this mitogen responsiveness, although PHA reactivity was less affected than Con A reactivity.