Figure 2.

Modes of progesterone signaling in the rodent. Classical progesterone receptor (PGR) can mediate progesterone signaling classically (A), by binding to DNA progesterone response elements. PGR can also be trafficked to the plasma membrane [as in (B)] where it can activate rapid intracellular signaling cascades involving kinases such as Src. It is unknown whether membrane PGR transactivates another receptor like an mGluR as estrogen receptors have been shown to do. Multiple novel membrane progesterone receptors (mPRs) have been recently discovered and described, such as mPRs α, β, δ, and γ (C). mPRs can activate signaling cascades via G proteins, which go on to affect cyclic AMP (cAMP) pathways. Finally, progestins can bind to progesterone receptor membrane component 1 [PGRMC1 (D)]. PGRMC1 can work in concert with SERBP1 to affect cAMP, Jak/Stat, and multiple kinase pathways (73).