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Expression of membrane progesterone receptors (mPRs) in rat peripheral glial cell membranes and their potential role in the modulation of cell migration and protein expression

Castelnovo, LF;Magnaghi, V;Thomas, P;

The role played by progestogens in modulating Schwann cell pathophysiology is well established. Progestogens exert their effects in these cells through both classical genomic and non-genomic mechanisms, the latter mediated by the GABA-A receptor. However, there is evidence that other receptors may be involved. Membrane progesterone receptors (mPRs) are novel 7-transmembrane receptors coupled to G proteins that have been characterized in different tissues and cells, including the central nervous system (CNS). The mPRs were shown to mediate some of progestogens’ neuroprotective effects in the CNS, and to be upregulated in glial cells after traumatic brain injury. Based on this evidence, this paper investigated the possible involvement of mPRs in mediating progestogen actions in S42 Schwann cells. All five mPR isoforms and progesterone receptor membrane component 1 (PGRMC1) were detected in Schwann cells, and were present on the cell membrane. Progesterone and the mPR-specific agonist, Org-OD-02-0 (02) bound to these membranes, indicating the presence of functional mPRs. The mPR agonist 02 rapidly increased cell migration in an in vitro assay, suggesting a putative role of mPRs in the nerve regeneration process. Treatment with pertussis toxin and 8-Br-cAMP blocked 02-induced cell migration, suggesting this progestogen action is mediated by activation of an inhibitory G protein, leading to a decrease in intracellular cAMP levels. In contrast, long-term mPR activation led to increased expression levels of myelin associated glycoprotein (MAG). Taken together, these findings show that mPRs are present and active in Schwann cells and have a role in modulating their physiological processes.