Neural progestin receptors and female sexual behavior

The steroid hormone, progesterone (P), modulates neuroendocrine functions in the central nervous system resulting in integration of reproduction and reproductive behaviors in female mammals. Although it is widely recognized that P's effects on female sex behavior are mediated by the classical neural progestin receptors (PRs) functioning as 'ligand-dependent' transcription factors to regulate genes and genomic networks, additional mechanisms of PR activation also contribute to the behavioral response. Cellular and molecular evidence indicates that PRs can be activated in a ligand-independent manner by neurotransmitters, growth factors, cyclic nucleotides, progestin metabolites and mating stimuli. The rapid responses of P may be mediated by a variety of PR types, including membrane-associated PRs or extranuclear PRs. Furthermore, these rapid nonclassical P actions involving cytoplasmic kinase signaling and/or extranuclear PRs also converge with classical PR-mediated transcription-dependent pathways to regulate reproductive behaviors. In this review, we summarize some of the history of the study of the role of PRs in reproductive behaviors and update the status of PR-mediated mechanisms involved in the facilitation of female sex behavior. We present an integrative model of PR activation via crosstalk and convergence of multiple signaling pathways.