br Acknowledgment Supported in part by NIH R EB

Acknowledgment Supported in part by NIH1R21EB012707 (Biegon, Anat PI).
Introduction Estrogens exert pleiotropic effects on a variety of morphological, physiological and behavioral responses in all vertebrate classes ranging from fishes to mammals. Effects of estrogens in the MM-102 concern reproductive behaviors (aggression, copulation, sexual differentiation, control of gonadotropins secretion) but also pain perception, language acquisition, various aspects of cognition (verbal and spatial memory, mood), as well as more broadly brain plasticity (neurogenesis, synaptogenesis, spinogenesis, angiogenesis, neuroprotection), cancer cell growth or immune function (Amandusson and Blomqvist, 2013; Au et al., 2016; Ervin et al., 2015; Fortress and Frick, 2014; Luine and Frankfurt, 2013; Marrocco and McEwen, 2016; Srivastava et al., 2013) (for more information see two full books on this topic: (Balthazart and Ball, 2013; Etgen and Pfaff, 2009)). It has long been thought that effects of estrogens on behavior rely on the same genomic mechanisms as morphological effects: estrogens regulate the expression of a variety of transmitters synthesizing or metabolizing enzymes and of neurotransmitters receptors, which in turn affect behavior expression. Estrogens like other steroids are indeed known to bind to intracellular receptors that then act as transcription factors to regulate gene expression (Jensen et al., 1968; McEwen and Alves, 1999). As such, these effects are relatively slow since they involve the transcription of specific genes into mRNA, their translation and then often posttranslational modifications of the resulting proteins and their incorporation into functional units (e.g. at the neuronal membrane). As a whole these processes take hours and sometimes days and as a result these genomic effects of steroid on behavior usually have latencies that range between a few hours and a few days. Faster actions of estrogens were however detected first at the cellular level (Kelly et al., 1976) (for reviews see: (McEwen, 1994; Schumacher, 1990)) and then more recently in terms of behavior control ((Cross and Roselli, 1999); reviews in (Balthazart and Ball, 2013; Cornil et al., 2012)). There was consequently a major paradigm shift in how we consider estrogens and more generally steroid action (Balthazart et al., 2018). Multiple reviews have dealt with this new way of thinking about steroid action (e.g. (Balthazart, 2017; Cornil et al., 2015; Foradori et al., 2008; Ronnekleiv and Kelly, 2017; Rudolph et al., 2016; Saldanha et al., 2011; Vasudevan and Pfaff, 2008). The current Special Issue of Hormones and Behavior focuses on these fast actions of estrogens, and more broadly of steroids, on brain and behavior. In this context, we review here recent data demonstrating rapid actions of estrogens on stimulus processing in animals considering in particular our recent work analyzing rapid estrogen action on auditory processing in songbirds as assessed by functional magnetic resonance imaging (fMRI)(De Groof et al., 2017).
Sex steroids and social communication Estradiol and testosterone have long been known to modulate both the production and the processing of external stimuli, in particular stimuli relevant to reproductive behaviors (Ball and Balthazart, 2009). It is for example clear that the production of rodent pheromones that control sexual interactions (Baum and Bakker, 2013; Petrulis, 2013) and the vocal activity of some fishes, amphibians and songbirds are markedly influenced by androgens and estrogens (Bass, 2008; Brenowitz, 2004, Brenowitz, 2008; Zornik and Kelley, 2011). Similarly, androgens drastically modify the electric organ discharges that are used by gymnotiform electric fishes for sex recognition (Bass and Zakon, 2005). Additionally, a host of studies demonstrate that steroids modify the perception and processing of sensory signals. This topic was recently covered in a special issue of Frontiers in Neuroendocrinology considering olfaction, vision, nociception and most importantly audition, which is the focus of this review (Balthazart, 2013). These effects of steroids are largely mediated by changes in the processing and interpretation of sensory signals by the brain, more than by changes in the sensory receptors themselves. There are only few examples where steroids were shown to modify the sensitivity or specificity of sensory detectors. One exception concerns neotropical electric fishes in which tuning of electrosensory receptors to changes in electrical organ discharges is affected by sex steroids. Similarly, estrogens modulate the inner ear capacity for encoding frequencies in female midshipman fishes, Porichthys notatus (Bass and Zakon, 2005). Accordingly, estrogen receptors and sometimes the estrogen producing enzyme, aromatase, are expressed in the inner ear of a wide variety of species ranging from fishes to birds, rodents and probably humans (Bass and Zakon, 2005; Chariditi and Canlon, 2010; Munaut et al., 2001; Noirot et al., 2009). Sex steroids could thus act directly on the inner ear but there is to date limited evidence that this is the case, possibly because this possibility has not been extensively investigated.