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), mPRalpha, mPRbeta, and mPRgamma 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 mPRalpha and mPRbeta but not mPRgamma, were detected by RT-PCR in PBLs, T lymphocytes, and Jurkat cells. Western blot analysis showed the presence of the mPRalpha and mPRbeta proteins on cell membranes of T lymphocytes and Jurkat cells. Expression of the mPRalpha 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.
Dosiou
C
C
Division of Endocrinology and Metabolism, Department of Medicine, Stanford University, Stanford, California 94305, USA.
Hamilton
A E
AE
Pang
Y
Y
Overgaard
M T
MT
Tulac
S
S
Dong
J
J
Thomas
P
P
Giudice
L C
LC
D000328:Adult; D002462:Cell Membrane / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D005434:Flow Cytometry; D019206:GTP-Binding Protein alpha Subunits, Gi-Go / Q000187:drug effects / Q000502:physiology; D019204:GTP-Binding Proteins / Q000187:drug effects* / Q000502:physiology; D015870:Gene Expression / Q000187:drug effects*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D007163:Immunosorbent Techniques; D019169:Jurkat Cells; D008183:Luteal Phase; D011374:Progesterone / Q000378:metabolism / Q000494:pharmacology*; D012333:RNA, Messenger / Q000032:analysis; D011980:Receptors, Progesterone / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013462:Sulfur Radioisotopes; D013601:T-Lymphocytes / Q000737:chemistry* / Q000378:metabolism
D012333:RNA, Messenger; D011980:Receptors, Progesterone; D013462:Sulfur Radioisotopes; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011374:Progesterone; D019204:GTP-Binding Proteins; D019206:GTP-Binding Protein alpha Subunits, Gi-Go