Expression of membrane progesterone receptors on human T lymphocytes and Jurkat cells and activation of G-proteins by progesterone

Although there is significant evidence for progesterone's. role as an immunomodulator, nuclear progesterone receptors have not been consistently identified in immune cells. Recently, three new putative membrane progesterone receptors (mPRs), mPR alpha, mPR beta, and mPR gamma have been described. The objective of this study was to examine whether mPRs are expressed in peripheral blood leukocytes (PBLs) in women of reproductive age, and to further characterize them in T lymphocytes and immortalized T cells Jurkat cells). Transcripts for mPR alpha and mPR beta but not mPR gamma, were detected by RT-PCP in PBLs, T lymphocytes, and Jurkat cells. Western blot analysis showed the presence of the mPR alpha and mPR beta proteins on cell membranes of T lymphocytes and Jurkat cells. Expression of the mPR alpha mRNA was upregulated in the luteal phase of the menstrual cycle in cluster of differentiation (CD)8(+), but not in CD4(+), T lymphocytes. Radioreceptor assays revealed specific [3 H]progesterone binding to T- and Jurkat cell membranes (K-d 4.25 nM) characteristic of steroid membrane receptors. Progesterone activated an inhibitory G-protein (G(i)), suggesting that mPRs are coupled to G(i) in Jurkat cells. These results suggest a potential novel mechanism for progesterone's immunoregulatory function through activation of mPRs.