Rapid and Widespread Effects of 17β-Estradiol on Intracellular Signaling in the Male Songbird Brain: A Seasonal Comparison

Abstract

Across vertebrate species, 17β-estradiol (E(2)) acts on the brain via both genomic and nongenomic mechanisms to influence neuronal physiology and behavior. Nongenomic E(2) signaling is typically initiated by membrane-associated estrogen receptors that modulate intracellular signaling cascades, including rapid phosphorylation of ERK. Phosphorylated ERK (pERK) can, in turn, rapidly phosphorylate tyrosine hydroxylase (TH) and cAMP response element-binding protein (CREB). Recent data suggest that the rapid effects of E(2) on mouse aggressive behavior are more prominent during short photoperiods (winter) and that acute aromatase inhibition reduces songbird aggression in winter only. To date, seasonal plasticity in the rapid effects of E(2) on intracellular signaling has not been investigated. Here, we compared the effects of acute (15 min) E(2) treatment on pERK, pTH, and pCREB immunoreactivity in male song sparrows (Melospiza melodia) pretreated with the aromatase inhibitor fadrozole during the breeding and nonbreeding seasons. We examined immunoreactivity in 14 brain regions including portions of the song control system, social behavior network, and the hippocampus (Hp). In both seasons, E(2) significantly decreased pERK in nucleus taeniae of the amygdala, pTH in ventromedial hypothalamus, and pCREB in mesencephalic central gray, robust nucleus of the arcopallium, and caudomedial nidopallium. However, several effects were critically dependent upon season. E(2) decreased pERK in caudomedial nidopallium in the breeding season only and decreased pCREB in the medial preoptic nucleus in the nonbreeding season only. Remarkably, E(2) decreased pERK in Hp in the breeding season but increased pERK in Hp in the nonbreeding season. Together, these data demonstrate that E(2) has rapid effects on intracellular signaling in multiple regions of the male brain and also demonstrate that rapid effects of E(2) can be profoundly different across the seasons.

Extra-gonadal steroids modulate non-breeding territorial aggression in weakly electric fish

“…The occurrence of non-breeding aggression has challenged the traditional paradigm of gonadal androgens as universal modulators of aggression. Recent elegant studies in mammals and birds have demonstrated that neurosteroids, particularly E2, play a major role in the regulation of non-breeding aggression (Charlier et al, 2011;Heimovics et al, 2012Heimovics et al, , 2015Pradhan et al, 2008Pradhan et al, , 2010Trainor et al, 2007Trainor et al, , 2008. To understand if this non-gonadal estrogenic control of aggression represents a general strategy among vertebrates, it is important to identify it in other classes of vertebrates, particularly in teleosts, which is the oldest and most diverse group of vertebrates.…”

“…These latter effects are likely mediated, at least in part, by actions on plasma membrane-bound receptors (Wehling and Lösel, 2006) or by allosteric modulation of neurotransmitter systems (Pinna et al, 2006). It has been suggested that non-genomic effects of E2 on aggressive behavior may be more prominent during the nonbreeding season, whereas the genomic effects of E2 on aggression may be more important during the breeding season (Heimovics et al, 2012(Heimovics et al, , 2015Trainor et al, 2007Trainor et al, , 2008. We observed a very significant effect on the aggressive behavior of G. omarorum after 1 h of a single administration of FAD.…”

“…Estrogens have been shown to be potent neurosteroids with Hormones and Behavior 72 (2015) 60-67 rapid effects Cornil et al, 2006;Pradhan et al, 2008Pradhan et al, , 2010Remage-Healey et al, 2010;Taziaux et al, 2007;Woolley, 2007) and can rapidly increase aggressive behavior and intracellular signaling in brain regions associated with social behavior with time courses that differ across seasons (Heimovics et al, 2012;Trainor et al, 2007Trainor et al, , 2008. Signaling pathways shift from predominately genomic mechanisms (effects in N30 min) in the breeding season, to mainly non-genomic ones (b30 min) in the non-breeding season (Heimovics et al, 2012(Heimovics et al, , 2015Trainor et al, 2007Trainor et al, , 2008. Together, these results call for the exploration of other taxa to understand if estrogenic regulation of non-breeding aggression is a general feature of vertebrates.…”

Rapid Effects of an Aggressive Interaction on Dehydroepiandrosterone, Testosterone and Oestradiol Levels in the Male Song Sparrow Brain: a Seasonal Comparison

“…Plasma was collected and stored at À20°C until radioimmunoassay. The Palkovits punch technique was used to microdissect brain tissue from six brain areas: the MSt, POA, AH, TnA, NCM and midbrain (17)(18)(19). Brains were sectioned in the coronal plane at 300 lm on a cryostat (À10°C) using a plane of sectioning that closely matched a zebra finch atlas (20).…”

The importance of neural aromatization in the acquisition, recall, and integration of song and spatial memories in passerines

“…2005; Hammes and Levin, 2007;Woolley, 2007) brain, as well as modifications in intracellular pathways similar to those in rodents (Frick, 2015) like pERK, pCREB, and Egr-1/ZENK (Cheng and Clayton, 2004;Maney et al, 2006;Heimovics et al, 2012). Additional studies could agonize or antagonize these receptors, inhibit components of specific signaling cascades, or measure their cellular and subcellular levels during phases in which birds -as indicated above -acquire, consolidate, retain, or recall the spatial tasks, to obtain a more comprehensive understanding of the postsynaptic mechanisms, specifically, that are downstream from the action of E 2 .…”