PROGESTERONE-INDUCED IMMUNOSUPPRESSION IS NOT MEDIATED THROUGH THE PROGESTERONE-RECEPTOR

Progesterone is a known immunosuppressant in humans and may be importa nt in treatment regimens for women with immunological and endocrinolog ical reproductive failure. The molecular mechanism of progesterone-med iated immunosuppression remains controversial. We used the reverse tra nscriptase polymerase chain reaction (RT-PCR) technique to detect prog esterone receptor RNA in human peripheral blood mononuclear cells (PBM Cs). No expression could be documented in PBMCs from men or women repr esenting various reproductive states. We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progestero ne exerts immuno-modulatory effects via interactions with the glucocor ticoid receptor. Both hydrocortisone (10(-6) and 10(-7) M) and progest erone (10(-5), 10(-6) and 10(-7) M) inhibited phytohaemagglutinin-indu ced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10 (-5) M) significantly reversed the immunosuppressive effect of hydroco rtisone but not that of progesterone. These studies indicate that huma n PBMCs do not express the classical progesterone receptor. Our result s further suggest that progesterone does not mediate its immunomodulat ory effects via interaction with the glucocorticoid receptor, Interact ion with other members of the steroid and thyroid hormone receptor sup erfamily, local conversion to other steroid substances or non-classica l receptor-mediated mechanisms may be involved.