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Human Reproduction, Vol. 11, No. 5, pp. 980-985, 1996
© 1996 European Society of Human Reproduction and Embryology

research-article

Progesterone-induced immunosuppression is not mediated through the progesterone receptor

D.J. Schust1, D.J. Anderson and J.A. Hill

The Fearing Research Laboratory, Divisions of Reproductive Immunology and Reproductive Medicine, Department of Obstetrics, Gynecology, and Reproductive Biology, Brigham and Women's Hospital, Harvard Medical School Boston, MA, USA

Correspondence: 1To whom correspondence should be addressed at: Fearing Research Laboratory, SGMB, Room 204, 250 Longwood Avenue, Boston, MA 02115, USA

Progesterone is a known immunosuppressant in humans and may be important in treatment regimens for women with immunological and endocrinological reproductive failure. The molecular mechanism of progesterone-mediated immunosuppression remains controversial. We used the reverse transcriptase polymerase chain reaction (RT-PCR) technique to detect progesterone receptor RNA in human peripheral blood mononuclear cells (PBMCs). No expression could be documented in PBMCs from men or women representing various reproductive states. We also used the glucocorticoid receptor antagonist RU 43044 to address the hypothesis that progesterone exerts immuno-modulatory effects via interactions with the glucocorticoid receptor. Both hydrocortisone (10–6 and 10–7 M) and progesterone (10–5, 10–6 and 10–7 M) inhibited phytohaemagglu-tinin-induced lymphocyte proliferation in a dose-dependent fashion. RU 43044 (10–5 M) significantly reversed the immunosuppressive effect of hydrocortisone but not that of progesterone. These studies indicate that human PBMCs do not express the classical progesterone receptor. Our results further suggest that progesterone does not mediate its immunomodulatory effects via interaction with the glucocorticoid receptor. Interaction with other members of the steroid and thyroid hormone receptor superfamily, local conversion to other steroid substances or non-classical receptor-mediated mechanisms may be involved.

Key words: human/immunosuppression/progesterone/receptor


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