Relationships between rapid changes in local aromatase activity and estradiol concentrations in male and female quail brain.
; ; Balthazart, Jacques et al
in Hormones and behavior (2014), 65(2), 154-164
Estradiol-17beta (E2) synthesized in the brain plays a critical role in the activation of sexual behavior in many vertebrate species. Because E2 concentrations depend on aromatization of testosterone ... [more ▼]
Estradiol-17beta (E2) synthesized in the brain plays a critical role in the activation of sexual behavior in many vertebrate species. Because E2 concentrations depend on aromatization of testosterone, changes in aromatase enzymatic activity (AA) are often utilized as a proxy to describe E2 concentrations. Utilizing two types of stimuli (sexual interactions and acute restraint stress) that have been demonstrated to reliably alter AA within minutes in opposite directions (sexual interactions=decrease, stress=increase), we tested in Japanese quail whether rapid changes in AA are paralleled by changes in E2 concentrations in discrete brain areas. In males, E2 in the pooled medial preoptic nucleus/medial portion of the bed nucleus of the stria terminalis (POM/BST) positively correlated with AA following sexual interactions. However, following acute stress, E2 decreased significantly (approximately 2-fold) in the male POM/BST despite a significant increase in AA. In females, AA positively correlated with E2 in both the POM/BST and mediobasal hypothalamus supporting a role for local, as opposed to ovarian, production regulating brain E2 concentrations. In addition, correlations of individual E2 in POM/BST and measurements of female sexual behavior suggested a role for local E2 synthesis in female receptivity. These data demonstrate that local E2 in the male brain changes in response to stimuli on a time course suggestive of potential non-genomic effects on brain and behavior. Overall, this study highlights the complex mechanisms regulating local E2 concentrations including rapid stimulus-driven changes in production and stress-induced changes in catabolism. [less ▲]Detailed reference viewed: 5 (0 ULg)
Endocrine disruptors: A relevant issue for neuroendocrinology also!
Balthazart, Jacques ;
in Frontiers in neuroendocrinology (2014), 35(1), 1Detailed reference viewed: 8 (1 ULg)
Reprint of: Policy decisions on endocrine disruptors should be based on science across disciplines: A response to Dietrich, et al.
; Balthazart, Jacques ; et al
in Frontiers in neuroendocrinology (2014), 35(1), 2-5Detailed reference viewed: 5 (1 ULg)
Estrogens control female sexual motivation and receptivity in quail.
de Bournonville, Catherine ; ; Balthazart, Jacques et al
Poster (2013, November 10)Detailed reference viewed: 14 (1 ULg)
c-fos down-regulation inhibits testosterone-dependent male sexual behavior and the associated learning
Niessen, Neville-Andrew ; Balthazart, Jacques ; et al
in European Journal of Neuroscience (2013)Detailed reference viewed: 16 (3 ULg)
Modulation of testosterone-dependent male sexual behavior and the associated neuroplasticity.
; Seredynski, Aurore ; Niessen, Neville-Andrew et al
in General and Comparative Endocrinology (2013)
Steroids modulate the transcription of a multitude of genes and ultimately influence numerous aspects of reproductive behaviors. Our research investigates how one single steroid, testosterone, is able to ... [more ▼]
Steroids modulate the transcription of a multitude of genes and ultimately influence numerous aspects of reproductive behaviors. Our research investigates how one single steroid, testosterone, is able to trigger this vast number of physiological and behavioral responses. Testosterone potency can be changed locally via aromatization into 17b-estradiol which then activates estrogen receptors of the alpha and beta subtypes. We demonstrated that the independent activation of either receptor activates different aspects of male sexual behavior in Japanese quail. In addition, several studies suggest that the specificity of testosterone action on target genes transcription is related to the recruitment of specific steroid receptor coactivators. We demonstrated that the specific down-regulation of the coactivators SRC-1 or SRC-2 in the medial preoptic nucleus by antisense techniques significantly inhibits steroid-dependent male-typical copulatory behavior and the underlying neuroplasticity. In conclusion, our results demonstrate that the interaction between several steroid metabolizing enzymes, steroid receptors and their coactivators plays a key role in the control of steroid-dependent male sexual behavior and the associated neuroplasticity in quail. [less ▲]Detailed reference viewed: 10 (0 ULg)
Neuroestrogens Rapidly Regulate Sexual Motivation But Not Performance
Seredynski, Aurore ; Balthazart, Jacques ; et al
in Journal of Neuroscience (2013), 33(1), 164-174
Estrogens exert pleiotropic effects on reproductive traits, which include differentiation and activation of reproductive behaviors and the control of the secretion of gonadotropins. Estrogens also ... [more ▼]
Estrogens exert pleiotropic effects on reproductive traits, which include differentiation and activation of reproductive behaviors and the control of the secretion of gonadotropins. Estrogens also profoundly affect non-reproductive traits, such as cognition and neuroprotection. These effects are usually attributed to nuclear receptor binding and subsequent regulation of target gene transcription. Estrogens also affect neuronal activity and cell-signaling pathways via faster, membrane-initiated events. How these two types of actions that operate in distinct timescales interact in the control of complex behavioral responses is poorly understood. Here, we show that the central administration of estradiol rapidly increases the expression of sexual motivation, as assessed by several measures of sexual motivation produced in response to the visual presentation of a female but not sexual performance in male Japanese quail. This effect is mimicked by membrane-impermeable analogs of estradiol, indicating that it is initiated at the cell membrane. Conversely, blocking the action of estrogens or their synthesis by a single intracerebroventricular injection of estrogen receptor antagonists or aromatase inhibitors, respectively, decreases sexual motivation within minutes without affecting performance. The same steroid has thus evolved complementary mechanisms to regulate different behavioral components (motivation vs performance) in distinct temporal domains (long- vs short-term) so that diverse reproductive activities can be properly coordinated to improve reproductive fitness. Given the pleiotropic effects exerted by estrogens, other responses controlled by these steroids might also depend on a slow genomic regulation of neuronal plasticity underlying behavioral activation and an acute control of motivation to engage in behavior. [less ▲]Detailed reference viewed: 53 (17 ULg)
Rapid control of reproductive behaviour by locally synthesised oestrogens: focus on aromatase.
Cornil, Charlotte ; Seredynski, Aurore ; de Bournonville, Catherine et al
in Journal of Neuroendocrinology (2013), 25(11), 1070-8
Oestrogens activate nucleus- and membrane-initiated signalling. Nucleus-initiated events control a wide array of physiological and behavioural responses. These effects generally take place within ... [more ▼]
Oestrogens activate nucleus- and membrane-initiated signalling. Nucleus-initiated events control a wide array of physiological and behavioural responses. These effects generally take place within relatively long periods of time (several hours to days). By contrast, membrane-initiated signalling affects a multitude of cellular functions in a much shorter timeframe (seconds to minutes). However, much less is known about their functional significance. Furthermore, the origin of the oestrogens able to trigger these acute effects is rarely examined. Finally, these two distinct types of oestrogenic actions have often been studied independently such that we do not exactly know how they cooperate to control the same response. The present review presents a synthesis of recent work carried out in our laboratory that aimed to address these issues in the context of the study of male sexual behaviour in Japanese quail, which is a considered as a suitable species for tackling these issues. The first section presents data indicating that 17b-oestradiol, or its membrane impermeable analogues, acutely enhances measures of male sexual motivation but does not affect copulatory behaviour. These effects depend on the activation of membrane-initiated events and local oestrogen production. The second part of this review discusses the regulation of brain oestrogen synthesis through post-translational modifications of the enzyme aromatase. Initially discovered in vitro, these rapid and reversible enzymatic modulations occur in vivo following variations in the social and environment context and therefore provide a mechanism of acute regulation of local oestrogen provision with a spatial and time resolution compatible with the rapid effects observed on male sexual behaviour. Finally, we discuss how these distinct modes of oestrogenic action (membrane- versus nucleus-initiated) acting in different time frames (short- versus long-term) interact to control different components (motivation versus performance) of the same behavioural response and improve reproductive fitness. [less ▲]Detailed reference viewed: 24 (1 ULg)
Neural pathways mediating control of reproductive behavior in male Japanese quail.
; Balthazart, Jacques
in The Journal of comparative neurology (2013), 521(9), 2067-87
The sexually dimorphic medial preoptic nucleus (POM) in Japanese quail has for many years been the focus of intensive investigations into its role in reproductive behavior. The present study delineates a ... [more ▼]
The sexually dimorphic medial preoptic nucleus (POM) in Japanese quail has for many years been the focus of intensive investigations into its role in reproductive behavior. The present study delineates a sequence of descending pathways that finally reach sacral levels of the spinal cord housing motor neurons innervating cloacal muscles involved in reproductive behavior. We first retrogradely labeled the motor neurons innervating the large cloacal sphincter muscle (mSC) that forms part of the foam gland complex (Seiwert and Adkins-Regan  Brain Behav Evol 52:61-80) and then putative premotor nuclei in the brainstem, one of which was nucleus retroambigualis (RAm) in the caudal medulla. Anterograde tracing from RAm defined a bulbospinal pathway, terminations of which overlapped the distribution of mSC motor neurons and their extensive dorsally directed dendrites. Descending input to RAm arose from an extensive dorsomedial nucleus of the intercollicular complex (DM-ICo), electrical stimulation of which drove vocalizations. POM neurons were retrogradely labeled by injections of tracer into DM-ICo, but POM projections largely surrounded DM, rather than penetrated it. Thus, although a POM projection to ICo was shown, a POM projection to DM must be inferred. Nevertheless, the sequence of projections in the male quail from POM to cloacal motor neurons strongly resembles that in rats, cats, and monkeys for the control of reproductive behavior, as largely defined by Holstege et al. (, Neuroscience 80:587-598). [less ▲]Detailed reference viewed: 2 (1 ULg)
Peripubertal proliferation of progenitor cells in the preoptic area of Japanese quail (Coturnix japonica).
; Balthazart, Jacques
in Brain research (2013), 1516
Brain structures related to reproduction are thought to depend on the action of gonadal steroids acting either during early life (organizing irreversible effects) or adulthood (activating transient ... [more ▼]
Brain structures related to reproduction are thought to depend on the action of gonadal steroids acting either during early life (organizing irreversible effects) or adulthood (activating transient effects). More recently puberty has become a focus of attention and it was demonstrated that action of sex steroid hormones at this time plays a critical role in the final organization of brain and behavior. We studied by BrdU immunohistochemistry the ontogeny from hatching to sexual maturity of a previously identified cell population in the preoptic area labeled by a BrdU injection at the end of embryonic period (E12) of sexual differentiation in male and female Japanese quail. After an initial increase between E12 and hatching, the density of BrdU-immunoreactive cells decreased until the beginning of puberty but then increased again during sexual maturation in the caudal preoptic area specifically. Divisions of these cells took place in the brain parenchyma as indicated by the large numbers of pairs of labeled cells. No sex difference affecting these processes could be detected at any stage of development. Large numbers of new cells thus arise around puberty in the caudal preoptic area and presumably contribute to the reorganization of this structure that precedes the emergence of adult reproductive behaviors. [less ▲]Detailed reference viewed: 3 (0 ULg)
A new method for in vitro detection of bromodeoxyuridine in serum: a proof of concept in a songbird species, the canary.
; ; et al
in PloS one (2013), 8(5), 63692
Systemic injection of a thymidine analogue such as bromodeoxyuridine (BrdU) in vertebrates is commonly used to detect and study cell production during development, adulthood, and pathology, particularly ... [more ▼]
Systemic injection of a thymidine analogue such as bromodeoxyuridine (BrdU) in vertebrates is commonly used to detect and study cell production during development, adulthood, and pathology, particularly in studies of adult neurogenesis. Although researchers are applying this technique to multiple species in various physiological conditions, the rate of BrdU clearance from the serum remains unknown in most cases. Changes in this clearance rate as a function of the species, sex or endocrine condition could however profoundly affect the interpretation of the results. We describe a rapid, sensitive, but simple bioassay for post-injection detection and quantification of BrdU in serum. This procedure was shown to be suitable for determining the length of time a thymidine analogue remains in the bloodstream of one avian species and seems applicable to any vertebrate provided sufficiently large blood samples can be collected. This technique was used to demonstrate that, in canaries, BrdU injected at a dose of 100 mg/kg is no longer available for incorporation into DNA between 30 and 60 min post-injection, a delay shorter than anticipated based on the available literature. Preliminary data suggest a similar fast clearance in Japanese quail and mice. [less ▲]Detailed reference viewed: 5 (0 ULg)
Anatomically discrete sex differences and enhancement by testosterone of cell proliferation in the telencephalic ventricle zone of the adult canary brain.
; ; Balthazart, Jacques
in Journal of chemical neuroanatomy (2013)
Previous work in songbirds has suggested that testosterone increases neuronal recruitment and survival in HVC but does not affect neuronal proliferation in the ventricular zone and that males and females ... [more ▼]
Previous work in songbirds has suggested that testosterone increases neuronal recruitment and survival in HVC but does not affect neuronal proliferation in the ventricular zone and that males and females have similar rates of proliferation except at discrete locations. Many of these conclusions are however based on limited data or were inferred indirectly. Here we specifically tested the effects of testosterone on cellular proliferation in the ventricular zone of both male and female adult canaries. We implanted adult birds of both sexes with testosterone or empty implants for 1 week and injected them with BrdU. One day later, we collected their brains and quantified BrdU-positive cells in the ventricular zone (VZ) at different rostro-caudal levels of the brain, ranging from the level where the song nucleus Area X occurs through the caudal extent of HVC. Proliferation in the dorsal part of the VZ was low and unaffected by sex or testosterone treatment. In the ventral part of the VZ, females had more proliferating cells than males, but only at rostral levels, near Area X. Also in the ventral part of the VZ, testosterone increased proliferation in birds of both sexes, but only in the mid- to caudal-VZ, caudal to the level of Area X, around the septum and HVC. We thus demonstrate here that there is both an effect of testosterone and possibly a more subtle effect of sex on cellular proliferation in the adult songbird brain, and that these effects are specific to different levels of the brain. [less ▲]Detailed reference viewed: 6 (0 ULg)
Differential effects of global versus local testosterone on singing behavior and its underlying neural substrate.
; Balthazart, Jacques ;
in Proceedings of the National Academy of Sciences of the United States of America (2013), 110(48), 19573-8
Steroid hormones regulate multiple but distinct aspects of social behaviors. Testosterone (T) has multiple effects on learned courtship song in that it regulates both the motivation to sing in a ... [more ▼]
Steroid hormones regulate multiple but distinct aspects of social behaviors. Testosterone (T) has multiple effects on learned courtship song in that it regulates both the motivation to sing in a particular social context as well as the quality of song produced. The neural substrate(s) where T acts to regulate the motivation to sing as opposed to other aspects of song has not been definitively characterized. We show here that T implants in the medial preoptic nucleus (POM) of castrated male canaries (Serinus canaria) increase song rate but do not enhance acoustic features such as song stereotypy compared with birds receiving peripheral T that can act globally throughout the brain. Strikingly, T action in the POM increased song control nuclei volume, consistent with the hypothesis that singing activity induces neuroplasticity in the song control system independent of T acting in these nuclei. When presented with a female canary, POM-T birds copulated at a rate comparable to birds receiving systemic T but produced fewer calls and songs in her presence. Thus, POM is a key site where T acts to activate copulation and increase song rate, an appetitive sexual behavior in songbirds, but T action in other areas of the brain or periphery (e.g., HVC, dopaminergic cell groups, or the syrinx) is required to enhance the quality of song (i.e., stereotypy) as well as regulate context-specific vocalizations. These results have broad implications for research concerning how steroids act at multiple brain loci to regulate distinct sociosexual behaviors and the associated neuroplasticity. [less ▲]Detailed reference viewed: 39 (12 ULg)
Distinct Neuroendocrine mechanisms control neural activity underlying sex differences in sexual motivation and performance
Balthazart, Jacques ; ; et al
in European Journal of Neuroscience (2013), 37(5), 735-42
Sexual behavior can be usefully parsed into an appetitive and a consummatory component. Both appetitive and consummatory male-typical sexual behaviors (respectively, ASB and CSB) are activated in male ... [more ▼]
Sexual behavior can be usefully parsed into an appetitive and a consummatory component. Both appetitive and consummatory male-typical sexual behaviors (respectively, ASB and CSB) are activated in male Japanese quail by testosterone (T) acting in the medial preoptic nucleus (POM), but never observed in females. This sex difference is based on a demasculinization (= organizational effect) by estradiol during embryonic life for CSB, but a differential activation by T in adulthood for ASB. Males expressing rhythmic cloacal sphincter movements (RCSMs; a form of ASB) or allowed to copulate display increased Fos expression in POM. We investigated Fos brain responses in females exposed to behavioral tests after various endocrine treat- ments. T-treated females displayed RCSM, but never copulated when exposed to another female. Accordingly they showed an increased Fos expression in POM after ASB but not CSB tests. Females treated with the aromatase inhibitor Vorozole in ovo and T in adulthood displayed both male-typical ASB and CSB, and Fos expression in POM was increased after both types of tests. Thus, the neural circuit mediating ASB is present or can develop in both sexes, but is inactive in females unless they are exposed to exogenous T. In contrast, the neural mechanism mediating CSB is not normally present in females, but can be pre- served by blocking the embryonic production of estrogens. Overall these data confirm the difference in endocrine controls and probably neural mechanisms supporting ASB and CSB in quail, and highlight the complexity of mechanisms underlying sexual differentiation of behavior. [less ▲]Detailed reference viewed: 14 (1 ULg)
RAPID MODULATION OF AROMATASE ACTIVITY IN THE VERTEBRATE BRAIN
; Cornil, Charlotte ; Balthazart, Jacques
in Journal of Experimental Neuroscience (2013)
Numerous steroid hormones, including 17-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the ... [more ▼]
Numerous steroid hormones, including 17-estradiol (E2), activate rapid and transient cellular, physiological, and behavioral changes in addition to their well-described genomic effects. Aromatase is the key-limiting enzyme in the production of estrogens, and the rapid modulation of this enzymatic activity could produce rapid changes in local E2 concentrations. The mechanisms that might mediate such rapid enzymatic changes are not fully understood but are currently under intense scrutiny. Recent studies in our laboratory indicate that brain aromatase activity is rapidly inhibited by an increase in intracellular calcium concentration resulting from potassium- induced depolarization or from the activation of glutamatergic receptors. Phosphorylating conditions also reduce aromatase activity within minutes, and this inhibition is blocked by the addition of multiple protein kinase inhibitors. This rapid modulation of aromatase activity by phosphorylating conditions is a general mechanism observed in different cell types and tissues derived from a variety of spe- cies, including human aromatase expressed in various cell lines. Phosphorylation processes affect aromatase itself and do not involve changes in aromatase protein concentration. The control of aromatase activity by multiple kinases suggests that several amino acids must be concomitantly phosphorylated to modify enzymatic activity but site-directed mutagenesis of several amino acids alone or in combination has not to date revealed the identity of the targeted residue(s). Altogether, the phosphorylation processes affecting aro- matase activity provide a new general mechanism by which the concentration of estrogens can be rapidly altered in the brain. [less ▲]Detailed reference viewed: 24 (2 ULg)
Neurochemical control of rapid stress-induced changes in brain aromatase activity
; Cornil, Charlotte ; Balthazart, Jacques
in Journal of Neuroendocrinology (2013), 25(4), 329-39
In the male brain, the medial preoptic nucleus (POM) is known to be a critical relay for the activation of sexual behaviour, with the aromatisation of testosterone into 17b-oestradiol (E2) playing a key ... [more ▼]
In the male brain, the medial preoptic nucleus (POM) is known to be a critical relay for the activation of sexual behaviour, with the aromatisation of testosterone into 17b-oestradiol (E2) playing a key role. Acute stress has been shown to differentially modulate the aromatase enzyme in this and other brain nuclei in a sex-specific manner. In POM specifically, stress induces increases in aromatase activity (AA) that are both rapid and reversible. How the physiological processes initiated during an acute stress response mediate sex- and nuclei- specific changes in AA and which stress response hormones are involved remains to be determined. By examining the relative effects of corticosterone (CORT), arginine vasotocin (AVT, the avian homologue to arginine vasopressin) and corticotrophin-releasing factor (CRF), the present study aimed to define the hormone profile regulating stress-induced increases in AA in the POM. We found that CORT, AVT and CRF all appear to play some role in these changes in the male brain. In addition, these effects occur in a targeted manner, such that modulation of the enzyme by these hormones only occurs in the POM rather than in all aromatase-expressing nuclei. Similarly, in the female brain, the experimental effects were restricted to the POM but only CRF was capable of inducing the stress-like increases in AA. These data further demonstrate the high degree of specificity (nuclei-, sex- and hormone-specific effects) in this system, highlighting the complexity of the stress–aromatase link and suggesting modes through which the nongenomic modulation of this enzyme can result in targeted, rapid changes in local oestrogen concentrations. [less ▲]Detailed reference viewed: 15 (0 ULg)
Dynamic changes in brain aromatase activity following sexual interactions in males: Where, when and why?
de Bournonville, Catherine ; ; et al
in Psychoneuroendocrinology (2013), 38(6), 789-99
It is increasingly recognized that estrogens produce rapid and transient effects at many neural sites ultimately impacting physiological and behavioral endpoints. The ability of estrogens to acutely ... [more ▼]
It is increasingly recognized that estrogens produce rapid and transient effects at many neural sites ultimately impacting physiological and behavioral endpoints. The ability of estrogens to acutely regulate cellular processes implies that their concentration should also be rapidly fine-tuned. Accordingly, rapid changes in the catalytic activity of aromatase, the limiting enzyme for estrogen synthesis, have been identified that could serve as a regulatory mechanism of local estrogen concentrations. However, the precise anatomical localization, time-course, triggering stimuli and functional significance of these enzymatic changes in vivo are not well understood. To address these issues as to where, when and why aromatase activity (AA) rapidly changes after sexual interactions, AA was assayed in six populations of aromatase-expressing cells microdissected from the brain of male quail that experienced varying durations of visual exposure to or copulation with a female. Sexual interactions resulted in a rapid AA inhibition. This inhibition occurred in specific brain regions (including the medial preoptic nucleus), in a context-dependent fashion and time-scale suggestive of post-translational modifications of the enzyme. Interestingly, the enzymatic fluctuations occurring in the preoptic area followed rather than preceded copulation and were tied specifically to the female's presence. This pattern of enzymatic changes suggests that rapid estrogen effects are important during the motivational phase of the behavior to trigger physiological events essential to activate mate search and copulation. [less ▲]Detailed reference viewed: 42 (11 ULg)
Cellular mechanisms controlling rapid changes in brain aromatase activity
; Cornil, Charlotte ; et al
in Balthazart, Jacques; Ball, Gregory (Eds.) Brain aromatase, estrogens and behavior (2012)Detailed reference viewed: 9 (0 ULg)
Rapid modulation of aromatase activity by social and environmental stimuli in quail
Cornil, Charlotte ; ; et al
in Balthazart, Jacques; Ball, Gregory (Eds.) Brain aromatase, estrogens and behavior (2012)Detailed reference viewed: 9 (0 ULg)