Differential effects of sex steroids on T and B cells: Modulation of cell cycle phase distribution, apoptosis and bcl-2 protein levels

Sex steroids have dramatic and differential effects on classic endocrine or gan proliferation and apoptosis. In this investigation we sought to delinea te similar effects of sex steroids on proliferation, cell cycle phase and a poptosis in lymphocyte cell lines as models for T and B cells. Estrogen and testosterone inhibited T cell line proliferation, induced accumulation of cells in S/G(2)M phases of the cell cycle, and increased apoptosis in a con centration-and time-dependent manner. There was a more modest effect of est rogen and testosterone on cell cycling and apoptosis in B lymphocyte cell l ines, suggesting that estrogen and testosterone are inhibitory to T but not B cell lines. In comparison, progesterone induced cytostasis and modestly increased apoptosis in both T and B cell lines. Estrogen and testosterone w ere not antagonistic or synergistic to each other in their effects on cell cycle phase distribution, and only minimally synergistic for apoptosis. In contrast, progesterone antagonized cell cycle and apoptotic effects of estr ogen in T cells. Estrogen-induced cell cycle and apoptotic effects in T cel l lines were associated with suppression of bcl-2 protein levels, which wer e unaffected in Raji B cells. Progesterone also antagonized the estrogen-in duced changes in T cell bcl-2 protein levels. These results suggest that th ere may be significant and differential sex steroid effects on T and B lymp hocytes that may be important to sexual dichotomies in immune and autoimmun e responses. Copyright (C) 2001 S. Karger AG, Basel.