Figure 2.

Schematic view of (A) estradiol and (B) progesterone signaling in neural cells through both classical and non-classical pathways. In the classical signaling pathway (right) the steroid hormone binds to its receptor located in the cytoplasm; the activated receptor dimerizes and makes its way into the nucleus where it interacts with responsive elements to activate or inhibit gene transcription. Also steroid hormones can bind to mitochondrial receptors that regulate mitochondrial DNA transcription. In the non-classical pathway (left) steroid hormones act through membrane receptors, including the classical receptors, GPCR receptors, ionotropic receptors, tyrosine kinase receptors, and other neurotransmitter receptors. This non-classical pathway initiates cytosolic signaling cascades, modulating the activation of various proteins and of second messenger systems. Additionally, progesterone and its metabolites promote myelination and remyelination at the oligodendrocyte level in the CNS and that of Schwann cells in the PNS.