| Summary: | 碩士 === 國立陽明大學 === 生理學研究所 === 99 === Background: Progesterone is an endogenous immunomodulator and can suppress T cell activation during pregnancy. However, there is no classical progesterone receptor, the nuclear progesterone receptor, in human peripheral T cells. In our previous studies, the expression of three new membrane progesterone receptors (mPRs, α, β, γ), which are G protein coupled receptors, and progesterone receptor membrane component 1 (PGRMC1) have been described in human peripheral T cells. In addition, progesterone induces intracellular calcium elevation and NHE1 inhibition resulting of acidification via T cell plasma membrane sites.
Methods: Fura-2 and BCECF were used to detect intracellular calcium concentration and pHi level; siRNA technology was used to determine the role of PGRMC1 in these pathways.
Results: Progesterone could stimulate intracellular calcium release from endoplasmic reticulum. Moreover, the intracellular calcium release was affected by thapsigargin (TG), U73122, 2-APB and SKF96365 and not by pertussis toxin, U73343, protein tyrosine kinase inhibitor, staurosporine, or PGRMC1 knockdown technology. These illustrated that progesterone stimulated intracellular calcium release was G protein coupled receptor dependent and not via PGRMC1. In addition, progesterone induced intracellular acidification but not NHE1 activity was prevented by BAPTA/AM, indicating that the presence of acidification by progesterone was not only dependent on NHE1 inhibition but also on the elevation of intracellular calcium. In Jurkat T cells, siRNA-mediated knock-down of PGRMC1 led to inhibit NHE1 activity and T cell proliferation.
Conclusions: progesterone induced calcium signal may be stimulated via progesterone membrane receptor, mPRs, and progesterone induced NHE1 inhibition and preventing T cell proliferation may associated with membrane receptor, PGRMC1.
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