RESUMO
The effect of gonadal steroids (GS) on proliferation of lymphocytes and distribution of lymphocyte subpopulations in cell culture was examined. The involvement of protein kinase C (PKC) and calcium ionophore in the proliferative response was tested. Estradiol benzoate (EB) or testosterone propionate (TP) had no significant influence on proliferation of peripheral blood lymphocytes (PBL) when cells were not stimulated by mitogen. At high concentration (10-6 M), EB and dihydrotestosterone (DHT) decreased lymphocyte proliferative response to concanavalin A (ConA) and lipopolysaccharide (LPS) at 24 and 72 h of incubation. However, at physiological doses (10(-12) to 10(-16) M), EB significantly enhanced the proliferative response at 24 h of incubation, whereas DHT had no effect. The inhibitory effect of the high dose of EB or DHT on proliferation of T and B lymphocytes was independent of time of hormone presentation to the cells or age and gender of cell donor. In all cultures, pre-incubation of lymphocytes with 10(-6) M of EB or DHT significantly reduced their proliferative responses to ConA, phytohemagglutinin (PHA), and LPS. The percentage of CD3+ cells was significantly reduced by EB, whereas DHT had no such effect. In contrast to inhibition of proliferation in response to mitogens, 10(-6) M EB dramatically enhanced the proliferation of lymphocytes in response to the PKC activator, phorbol 12-myristate 13-acetate, and calcium ionophore, A23187. Results suggest that high doses of EB do not damage the viability or proliferation capability of lymphocytes and, therefore, suppress the proliferative response to mitogens in a different manner, perhaps by reducing gene transcription for receptors that recognize the mitogens, or suppressing some postreceptor events. The enhancement of proliferation in response to mitogens by low doses of EB may support this assumption, because the biphasic effects of steroids on gene transcription are well documented.