Neural Progestin Receptors and Female Sexual Behavior

Abstract

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.

Sex Hormones and Cognition: Neuroendocrine Influences on Memory and Learning

“…Progesterone receptors (PRs) are located in a variety of brain regions, including the CA3 region of the hippocampus, and are expressed in two isoforms PR-A and PR-B (403). PR expression is induced by estradiol in adult female rodents in many regions of the brain including the amygdala, medial preoptic area, and regions of the hypothalamus and the hippocampus (403).…”

“…It is also important to bear in mind that progesterone initially enhances estradiol-induced sexual receptivity in female rodents, but then serves to terminate receptivity and induce sexual refractoriness 24 h later (450). Mechanistically, this effect on sexual behavior is initiated by estradiol as systemic treatment increases the expression of PRs in regions associated with reproductive behavior such as the hypothalamus (396), amygdala, medial preoptic area (403), and spinal cord (436). As noted earlier PR expression is induced by estradiol even in the hippocampus, thus perhaps it should not be surprising that there may be biphasic effects of progesterone on cognition, depending on background estradiol levels (and PR expression) (403).…”

Variation in Progesterone Receptors and GnRH Expression in the Hypothalamus of the Pregnant South American Plains Vizcacha, Lagostomus maximus (Mammalia, Rodentia)1

“…This is assumed to be the primary pathway for P4 action in the brain. However, nongenomic actions of PR have been recently described [38]. Cytoplasmic second messenger signaling cascades involving extranuclear PR that interacts with Src kinase via MAPK action can increase the phosphorylation of coactivators that act as transcription factors [39,40].…”

Sex Hormones and Alzheimer’s Disease

“…It has many reproductive and non-reproductive functions, including regulation of a wide range of brain functions [48]. Progesterone has a lipophilic structure, which can cross the cell membrane to interact with its specific intracellular progesterone receptors (PRs) expressed throughout the brain without sex difference with special higher expression in the hypothalamus, hippocampus, frontal cortex, medial amygdaloid nucleus, norepinephrine neurons of the nucleus tractus solitaries and cerebellum.…”