Rapid regulation by glutamate of aromatase activity
Charlier, Thierry ; ; Balthazart, Jacques
Poster (2011)Detailed reference viewed: 8 (0 ULg)
Rapid increase in aggressive behavior precedes the decrease in brain aromatase activity during socially mediated sex change in Lythrypnus dalli.
; Balthazart, Jacques ; et al
in General and Comparative Endocrinology (2011), 170(1), 119-24
In the bluebanded goby, Lythrypnus dalli, removal of the male from a social group results in a rapid behavioral response where one female becomes dominant and changes sex to male. In a previous study ... [more ▼]
In the bluebanded goby, Lythrypnus dalli, removal of the male from a social group results in a rapid behavioral response where one female becomes dominant and changes sex to male. In a previous study, within hours of male removal, aromatase activity in the brain (bAA) of dominant females was almost 50% lower than that of control females from a group in which the male had not been removed. For those females that displayed increased aggressive behavior after the male was removed, the larger the increase in aggressive behavior, the greater the reduction in bAA. To investigate whether decreased bAA leads to increased aggression, the present study used a more rapid time course of behavioral profiling and bAA assay, looking within minutes of male removal from the group. There were no significant differences in bAA between control females (large females from groups with the male still present), females that doubled their aggressive behavior by 10 or 20 min after male removal, or females that did not double their aggressive behavior within 30 min after male removal. Further, individual variation in bAA and aggressive behavior were not correlated in these fish. Whole brain decreases in aromatase activity thus appear to follow, rather than precede, rapid increases in aggressive behavior, which provides one potential mechanism underlying the rapid increase in androgens that follows aggressive interactions in many vertebrate species. For fish species that change sex from female to male, this increase in androgens could subsequently facilitate sex change. [less ▲]Detailed reference viewed: 14 (3 ULg)
Effects of sex steroids on aromatase mRNA expression in the male and female quail brain.
; ; Balthazart, Jacques
in General and Comparative Endocrinology (2011), 170(1), 180-8
Castrated male quail display intense male-typical copulatory behavior in response to exogenous testosterone but ovariectomized females do not. The behavior of males is largely mediated by the central ... [more ▼]
Castrated male quail display intense male-typical copulatory behavior in response to exogenous testosterone but ovariectomized females do not. The behavior of males is largely mediated by the central aromatization of testosterone into estradiol. The lack of behavioral response in females could result from a lower rate of aromatization. This is probably not the case because although the enzymatic sex difference is clearly present in gonadally intact sexually mature birds, it is not reliably found in gonadectomized birds treated with testosterone, in which the behavioral sex difference is always observed. We previously discovered that the higher aromatase activity in sexually mature males as compared to females is not associated with major differences in aromatase mRNA density. A reverse sex difference (females>males) was even detected in the bed nucleus of the stria terminalis. We analyzed here by in situ hybridization histochemistry the density of aromatase mRNA in gonadectomized male and female quail that were or were not exposed to a steroid profile typical of their sex. Testosterone and ovarian steroids (presumably estradiol) increased aromatase mRNA concentration in males and females respectively but mRNA density was similar in both sexes. A reverse sex difference in aromatase mRNA density (females>males) was detected in the bed nucleus of subjects exposed to sex steroids. Together these data suggest that although the induction of aromatase activity by testosterone corresponds to an increased transcription of the enzyme, the sex difference in enzymatic activity results largely from post-transcriptional controls that remain to be identified. [less ▲]Detailed reference viewed: 54 (2 ULg)
Sexual arousal, is it for mammals only?
; Balthazart, Jacques
in Hormones and Behavior (2011), 59(5), 645-55
Sexual arousal has many dimensions and has consequently been defined in various ways. In humans, sexual arousal can be assessed based in part on verbal communication. In male non-human mammalian species ... [more ▼]
Sexual arousal has many dimensions and has consequently been defined in various ways. In humans, sexual arousal can be assessed based in part on verbal communication. In male non-human mammalian species, it has been argued that arousal can only be definitively inferred if the subject exhibits a penile erection in a sexual context. In non-mammalian species that lack an intromittent organ, as is the case for most avian species, the question of how to assess sexual arousal has not been thoroughly addressed. Based on studies performed in male Japanese quail, we argue that several behavioral or physiological characteristics provide suitable measures of sexual arousal in birds and probably also in other tetrapods. These indices include, the performance of appetitive sexual behavior in anticipation of copulation (although anticipation and arousal are not synonymous), the activation of specific brain area as identified by the detection of the expression of immediate early genes (fos, egr-1) or by 2-deoxygucose quantitative autoradiography, and above all, by the release of dopamine in the medial preoptic area as measured by in vivo dialysis. Based on these criteria, it is possible to assess in birds sexual arousal in its broadest sense but meeting the more restrictive definition of arousal proposed for male mammals (erection in an explicit sexual context) is and will probably remain impossible in birds until refinement of in vivo imaging techniques such fMRI allow us to match in different species, with and without an intromittent organ, the brain areas that are activated in the presence of specific stimuli. [less ▲]Detailed reference viewed: 12 (4 ULg)
Sex differences in the rapid control of aromatase activity in the quail preoptic area.
; Balthazart, Jacques
in Journal of Neuroendocrinology (2011), 23(5), 424-34
Adult male quail show high levels of aromatase activity in the preoptic area-hypothalamus (POA-HYP), which parallels the high number of aromatase-immunoreactive cells and elevated mRNA concentrations ... [more ▼]
Adult male quail show high levels of aromatase activity in the preoptic area-hypothalamus (POA-HYP), which parallels the high number of aromatase-immunoreactive cells and elevated mRNA concentrations detected in this brain region by in situ hybridisation. Interestingly, females display considerably lower aromatase activity than males but have almost equal numbers of aromatase-immunoreactive cells and express similar levels of aromatase mRNA. Aromatase activity in the male POA-HYP can be rapidly regulated by calcium-dependent phosphorylations, in the absence of changes in enzyme concentration. In the present study, we investigated whether aromatase activity is differentially regulated by phosphorylations in males and females. A linear increase in accumulation of aromatisation products was observed in both sexes as a function of time but the rate of conversion was slower in females. Saturation analysis confirmed the lower maximum velocities (V(max) ) in females but indicated a similar affinity (K(m) ) in both sexes. Aromatase activity in females reacted differentially to manipulations of intracellular calcium. In particular, chelating calcium with ethylene glycol tetraacetic acid (EGTA) resulted in a larger increase of enzymatic activity in males than in females, especially in the presence of ATP. A differential reaction to kinase inhibitors was also observed between males and females (i.e. a larger increase in aromatase activity in females than in males after exposure to specific inhibitors). These findings suggest that the nature of aromatase is conserved between the sexes, although the control of its activity by calcium appears to be different. Additional characterizations of intracellular calcium in both sexes would therefore be appropriate to better understand aromatase regulation. [less ▲]Detailed reference viewed: 83 (4 ULg)
Sexual differentiation of sexual behavior and its orientation.
; Balthazart, Jacques
in Frontiers in Neuroendocrinology (2011), 32(2), 109Detailed reference viewed: 42 (10 ULg)
Minireview: Hormones and Human Sexual Orientation.
in Endocrinology (2011)
Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal ... [more ▼]
Many people believe that sexual orientation (homosexuality vs. heterosexuality) is determined by education and social constraints. There are, however, a large number of studies indicating that prenatal factors have an important influence on this critical feature of human sexuality. Sexual orientation is a sexually differentiated trait (over 90% of men are attracted to women and vice versa). In animals and men, many sexually differentiated characteristics are organized during early life by sex steroids, and one can wonder whether the same mechanism also affects human sexual orientation. Two types of evidence support this notion. First, multiple sexually differentiated behavioral, physiological, or even morphological traits are significantly different in homosexual and heterosexual populations. Because some of these traits are known to be organized by prenatal steroids, including testosterone, these differences suggest that homosexual subjects were, on average, exposed to atypical endocrine conditions during development. Second, clinical conditions associated with significant endocrine changes during embryonic life often result in an increased incidence of homosexuality. It seems therefore that the prenatal endocrine environment has a significant influence on human sexual orientation but a large fraction of the variance in this behavioral characteristic remains unexplained to date. Genetic differences affecting behavior either in a direct manner or by changing embryonic hormone secretion or action may also be involved. How these biological prenatal factors interact with postnatal social factors to determine life-long sexual orientation remains to be determined. [less ▲]Detailed reference viewed: 66 (14 ULg)
Specific activation of estrogen recepto alpha and beta enhances male sexual behavior and neuroplasticity in male Japanese quail
Seredynski, Aurore ; ; Balthazart, Jacques et al
in PLoS ONE (2011), 6(4), 18627Detailed reference viewed: 18 (6 ULg)
Role of estrogen receptors alpha and beta on sexual behavior and neuroplasticity in male Japanese quail
Seredynski, Aurore ; Balthazart, Jacques ; Charlier, Thierry
Poster (2011)Detailed reference viewed: 20 (8 ULg)
Own song selectivity in the songbird auditory pathway: Suppression by norepinephrine
; ; et al
in PLoS ONE (2011), 6(5), 20131Detailed reference viewed: 17 (2 ULg)
Rapid activation of phosphorylated mitogen-activated protein kinase after sexual stimulation in male mice.
; ; Balthazart, Jacques et al
in Neuroreport (2011), 22(6), 294-8
We mapped cells immunoreactive for the phosphorylated form (p44/p42) of the mitogen-activated protein kinase (pMAPK--also known as ERK1/2) in the brain of male mice after exposure to female olfactory cues ... [more ▼]
We mapped cells immunoreactive for the phosphorylated form (p44/p42) of the mitogen-activated protein kinase (pMAPK--also known as ERK1/2) in the brain of male mice after exposure to female olfactory cues or after the display of male copulatory behaviors. Exposure to soiled bedding from estrous females or the display of coital behaviors rapidly (within 10 min) induced MAPK phosphorylation in most of the brain regions known to be involved in the processing of olfactory cues (main and accessory olfactory bulbs, amygdala, and medial preoptic area) and in the control of copulatory behavior (amygdala and medial preoptic area). MAPK phosphorylation thus seems to be a useful marker to study short-term neural activation associated with the expression of specific behaviors. [less ▲]Detailed reference viewed: 12 (0 ULg)
The steroid receptor coactivators SRC-1 and CARM1 expression is modulated during different phases of neurogenesis in the dentate gyrus of adult female rats
Charlier, Thierry ; ; et al
Poster (2011)Detailed reference viewed: 19 (4 ULg)
Steroid receptor coactivator 2 (SRC-2) mediates steroid-dependent male sexual behavior and neuroplasticity in Japanese quail (Coturnix japonica)
Niessen, Neville-Andrew ; Balthazart, Jacques ; Charlier, Thierry
Poster (2011)Detailed reference viewed: 17 (5 ULg)
Androgens and estrogens synergistically regulate the expression of doublecortin and enhance neuronal recruitment in the song system of adult female canaries.
; Barker, Jennifer ; Balthazart, Jacques et al
in Journal of Neuroscience (2011)
Vocal control nuclei in songbirds display seasonal changes in volume that are regulated by testosterone (T) and its androgenic (5α-dihydrotestosterone; DHT) or estrogenic metabolites (17β-estradiol; E2 ... [more ▼]
Vocal control nuclei in songbirds display seasonal changes in volume that are regulated by testosterone (T) and its androgenic (5α-dihydrotestosterone; DHT) or estrogenic metabolites (17β-estradiol; E2). In male canaries, T regulates expression of the microtubule-associated protein doublecortin (DCX), a marker of neurogenesis. We examined the effect of T and its two metabolites alone or in combination on DCX expression in adult female canaries. Treatment with T or with DHT+E2 increased HVC volume and neuron numbers as well as the total numbers of fusiform (migrating) and round (differentiating) DCX neurons in the nucleus but generally not in adjacent areas. DHT or E2 alone did not increase these measures but increased the density of fusiform DCX cells per section. Similar results were observed in Area X although some effects did not reach significance presumably because plasticity in X is mediated transynaptically and follows HVC changes with some delay. There was no effect of any treatment on the total number of neurons in Area X and no change in DCX cell densities was detected in other parts of the nidopallium nor in LMAN. DHT and E2 by themselves thus increase density of DCX cells migrating through HVC but are not sufficient in isolation to induce the recruitment of these newborn neurons in the nucleus. These effects are generally not observed in the rest of the nidopallium implying that steroids only act on the attraction and recruitment of new neurons in HVC without having any major effects on their production at the ventricle wall. [less ▲]Detailed reference viewed: 17 (0 ULg)
Auditory forebrain activation in the female canary is modulated by male song quality.
Barker, Jennifer ; ; et al
Poster (2010, November 17)
One of the chief functions of birdsong is to attract and stimulate females. In canaries (Serinus canaria), speciﬁc phrases (“A” phrases) sung by males have been identiﬁed as especially attractive for ... [more ▼]
One of the chief functions of birdsong is to attract and stimulate females. In canaries (Serinus canaria), speciﬁc phrases (“A” phrases) sung by males have been identiﬁed as especially attractive for females. These phrases unite a number of characteristics that are particularly difﬁcult to combine, including large frequency bandwidth, high repetition rate and multiple-note syllables. Females exposed to “A” phrases produce more copulation displays and deposit more testosterone into their eggs. However, the neuroendocrine pathway underlying the translation of song audition to changes in testosterone deposition in yolks is not understood. Increased expression of several immediate early genes including c-fos and zenk (also called egr-1 in mammals) in other songbird species has been observed in the auditory forebrain of females hearing attractive song, and such differential activation may represent a ﬁrst step in signal processing linking auditory input to egg testosterone deposition. Female canaries in breeding condition were exposed to 60 minutes of “sexy” song with a preponderance of “A” phrases, “non-sexy” song lacking “A” phrases, or white noise. Thirty minutes after the end of song playback, brains were collected, ﬁxed in acrolein and sectioned and stained by immunohistochemistry for quantiﬁcation of the Fos protein, an indicator of neuronal activity, in several regions involved in audition and auditory processing. The endocrine condition of each female was determined by measuring ovarian and oviduct weight at the time of autopsy. In the caudomedial mesopallium (CMM), Fos expression was higher in females that had heard sexy song than those that heard non-sexy song or white noise. Expression of Fos in the caudomedial nidopallium (NCM), the nucleus spiriformis medialis (SPM), the nucleus ovoidalis (OV), and the song nucleus HVC was unaffected by song quality. Thus differential auditory processing in the CMM may be an initial stage in the assessment by a female of song information to differential testosterone deposition in the egg. [less ▲]Detailed reference viewed: 21 (2 ULg)
Sexually differentiated cell proliferation in the medial preoptic nucleus of Japanese quail
Mouriec, Karen ; ; Balthazart, Jacques
Poster (2010, November)
The androgen-depend sequence of male copulatory behaviors is sexually differentiated in Japanese quail like in many other vertebrates. This behavior disappears within a week after castration of males and ... [more ▼]
The androgen-depend sequence of male copulatory behaviors is sexually differentiated in Japanese quail like in many other vertebrates. This behavior disappears within a week after castration of males and is rapidly restored following treatment with testosterone. In contrast, ovariectomized females treated with testosterone never show these behaviors. This sex-specific responsiveness to testosterone results from organizational effects of embryonic ovarian estrogens. The behavioral phenotype of male and female quail is completely reversed by treatment, before embryonic day 12 (E12), of male embryos with estrogens or of female embryos with an inhibitor of aromatase, the enzyme converting testosterone into estradiol. In the quail brain, the medial preoptic nucleus (POM) is a necessary and sufficient site for the activation of sexual behavior by testosterone. It can be identified by a dense population of aromatase-immunoreactive neurons and, importantly, aromatase activity in this region is sexually differentiated (males>females) and this difference is maintained even when birds are treated with a same dose of testosterone. Aromatase is thus, like sexual behavior, a sex-specific feature regulated by testosterone in adult quail and presumably organized in early life by steroid action. The cellular basis of these organizational processes have not been identified. We analyzed the ontogeny of POM cells by injecting 5-bromo-2-deoxyuridine (BrdU) in eggs at different embryonic (E) stages (E8, E10, E12, E14 and E16) and quantifying BrdU-labeled cells at postnatal (PN) day 56. Large numbers of BrdU-positive cells were observed throughout the POM of males and females injected on E8-E10 but most cells were post-mitotic in both sexes on E14-E16. E12 injections resulted in a larger number of BrdU cells in females than in males at PN56. However, male and female embryos injected on E12 and killed on E13, PN1 or PN15 had similar numbers of BrdU positive cells. Furthermore, BrdU injections on E14 labeled very few cells at PN 56 suggesting that the POM is essentially post-mitotic at that age. Together these data suggest that a sex-specific apoptosis must occur between PN15 and PN56. Double-label immunohistochemistry for BrdU and for the neuron-specific marker Hu indicated that BrdU-positive cells born between E8 and E16 are not neurons and are thus presumably glial cells. This sex-specific cell proliferation occurring around the end of the critical period of sexual differentiation may have an important impact on brain and behavior differentiation. The phenotype of these cells and the mechanisms mediating their differential development are currently under investigation. [less ▲]Detailed reference viewed: 15 (1 ULg)
Ontogeny of sex differences in steroid-sensitive regions in the quail brain (Coturnix Japonica)
Mouriec, Karen ; ; Balthazart, Jacques
Poster (2010, May)
Sex differences affecting the expression of sexual behavior are observed in many species. In quail, expression of the male-typical copulatory pattern is androgen-dependent. This behavior disappears within ... [more ▼]
Sex differences affecting the expression of sexual behavior are observed in many species. In quail, expression of the male-typical copulatory pattern is androgen-dependent. This behavior disappears within a week after castration and is restored after a few days of treatment with exogenous testosterone. In contrast, ovariectomized females treated with testosterone never show the sequence of male-typical copulatory behavior. This sex difference in responsiveness to testosterone results from organizational effects of embryonic estrogens secreted by the female ovary. The behavioral phenotype can be completely reversed by treatment, before embryonic day 12, of male embryos with estrogens or of female embryos with an aromatase inhibitor. In the quail brain, the medial preoptic nucleus (POM) is a necessary and sufficient site for the activation by testosterone of sexual behavior. Aromatase, the enzyme converting testosterone into estradiol, is densely expressed in POM and its activity is sexually differentiated (males>females) even when birds are treated with a same dose of testosterone. Aromatase and other neuroendocrine systems are thus, like sexual behavior, differentially activated by testosterone in adult quail but the cellular basis of these sexually differentiated features presumably organized in early life by steroid action have not been identified. To analyze the ontogeny of steroid sensitive regions that control behavioral sex differences in the quail brain, we injected 5-bromo-2-deoxyuridine (BrdU) in eggs at different stages of the embryonic (E) development (E8, E10, E12, E14 and E16) and sacrificed the animals at postnatal (PN) day 56. Large numbers of BrdU-positive cells were observed throughout the POM of males and females injected on E8-E10 but most cells were post-mitotic in both sexes on E14-E16. E12 injections resulted in a larger number of BrdU cells in females than in males. This differential number of BrdU-positive cells seen at PN56 in birds injected on E12 could result from a) a difference in the age at which cells become post-mitotic (males before females or alternatively females before males, so that male cells labeled by BrdU on E12 dilute their label in subsequent divisions) or b) a differential apoptosis between E13 and PN56. However, no sex differences in the number of BrdU positive cells was observed in embryos injected with BrdU on E12 and killed on E13. Furthermore, BrdU injections on E14 labeled very few cells at PN 56 suggesting that the POM is essentially post-mitotic at that age. The sex difference observed in birds injected at E12 should result from a differential apoptosis after E13. Double-label immunohistochemistry for BrdU and the neuronal marker Hu (C/D) indicated that all BrdU-positive cells born between E8 and E16 are not neurons (no double label) suggesting that these are glial cells. This sex difference in (glial?) proliferation around the end of the critical period of sexual differentiation may play a key role in the differentiation of brain and behavior. The specific phenotype of these cells and the mechanisms mediating their differential development are currently under investigation. [less ▲]Detailed reference viewed: 23 (1 ULg)
Testosterone increases cell turnover in song nucleus HVC and increases cell recruitment into Area X of adult female canaries.
Barker, Jennifer ; ; Balthazart, Jacques et al
Poster (2010, May)
In songbirds, song control nuclei such as HVC and Area X, show seasonal changes in volume that are regulated, at least in part, by the action of gonadal testosterone (T) and its metabolites. These changes ... [more ▼]
In songbirds, song control nuclei such as HVC and Area X, show seasonal changes in volume that are regulated, at least in part, by the action of gonadal testosterone (T) and its metabolites. These changes in volume are a result of changes in cell size, dendritic branching and, in HVC, the incorporation of newborn neurons. Doublecortin (DCX) is a microtubule-associated protein expressed during development and in adulthood in post-mitotic migrating and differentiating neurons in mammals. Our previous studies in male canaries demonstrated that DCX is expressed in BrdU-positive neurons consistent with DCX being a marker of neurogenesis in adult canaries. Testosterone induces marked increases in song nuclei volume in adult female canaries making these nuclei more male-like. Within the songbird brain, T can be metabolized to 5 alpha-dihydrotestosterone (DHT) and 17 beta-estradiol (E2). We found previously that both these metabolites are required to increase the volume of song nuclei in adult female canaries, but the cellular basis of this adult neuroplasticity is not well understood. Within HVC, the number of DCX-immunoreactive (ir) cells can be increased by photostimulation or treatment with T, but the effects of T and its metabolites on cell death in the songbird brain had not yet been elucidated. We therefore examined the effect of DHT and E2 on DCX expression and cell death in the song nuclei of adult female canaries. Intact female canaries were implanted with Silastic tubing containing crystalline T, DHT, E2, or a combination of DHT+E2. Control animals received empty implants. All birds were kept under early spring-like photoperiodic conditions (11L:13D) for 3 weeks. In HVC, the total number of DCX-ir cells was increased by treatment with T or DHT+E2 as compared to control birds, but was not affected by treatment with DHT or E2 alone. The number of pyknotic cells observed in the HVC was also increased by T but not by its metabolites. In Area X, the total number of DCX-ir cells was increased by treatment with T or DHT+E2, but the number of pyknotic cells was unaffected by hormone treatment. These results suggest that T enhances cellular turnover in the HVC (migration into, and cell death within, HVC), but affects only recruitment of new neurons into Area X. [less ▲]Detailed reference viewed: 52 (3 ULg)
Japanese quail as a model system for studying the neuroendocrine control of reproductive and social behaviors.
; Balthazart, Jacques
in ILAR Journal (2010), 51(4), 310-25
Japanese quail (Coturnix japonica; referred to simply as quail in this article) readily exhibit sexual behavior and related social behaviors in captive conditions and have therefore proven valuable for ... [more ▼]
Japanese quail (Coturnix japonica; referred to simply as quail in this article) readily exhibit sexual behavior and related social behaviors in captive conditions and have therefore proven valuable for studies of how early social experience can shape adult mate preference and sexual behavior. Quail have also been used in sexual conditioning studies illustrating that natural stimuli predict successful reproduction via Pavlovian processes. In addition, they have proven to be a good model to study how variation in photoperiod regulates reproduction and how variation in gonadal steroid hormones controls sexual behavior. For example, studies have shown that testosterone activates male-typical behaviors after being metabolized into estrogenic and androgenic metabolites. A critical site of action for these metabolites is the medial preoptic nucleus (POM), which is larger in males than in females. The enzyme aromatase converts testosterone to estradiol and is enriched in the POM in a male-biased fashion. Quail studies were the first to show that this enzyme is regulated both relatively slowly via genomic actions of steroids and more quickly via phosphorylation. With this base of knowledge and the recent cloning of the entire genome of the closely related chicken, quail will be valuable for future studies connecting gene expression to sexual and social behaviors. [less ▲]Detailed reference viewed: 15 (2 ULg)
Diversity of mechanisms involved in aromatase regulation and estrogen action in the brain
Charlier, Thierry ; Cornil, Charlotte ; et al
in Biochimica et Biophysica Acta - General Subjects (2010)
Background In recent years, the mechanisms through which estrogens modulate neuronal physiology, brain morphology, and behavior have proven to be far more complex than previously thought. For example, a ... [more ▼]
Background In recent years, the mechanisms through which estrogens modulate neuronal physiology, brain morphology, and behavior have proven to be far more complex than previously thought. For example, a second nuclear estrogen receptor has been identified, a new family of coregulatory proteins regulating steroid-dependent gene transcriptions was discovered and, finally, it has become clear that estrogens have surprisingly rapid effects based on their actions on cell membranes, which in turn result in the modulation of intracellular signaling cascades. Scope of review This paper presents a selective review of new findings in this area related to work in our laboratories, focusing on the role of estrogens in the activation of male sexual behavior. Two separate topics are considered. We first discuss functions of the steroid receptor coactivator-1 (SRC-1) that has emerged as a key limiting factor for behavioral effects of estradiol. Knocking-down its expression by antisense oligonucleotides drastically inhibits male-typical sexual behaviors. Secondly, we describe rapid regulations of brain estradiol production by calcium-dependent phosphorylations of the aromatase enzyme, themselves under the control of neurotransmitter activity. These rapid changes in estrogen bioavailability have clear behavioral consequences. Increases or decreases in estradiol concentrations respectively obtained by an acute injection of estradiol itself or of an aromatase inhibitor lead within 15–30 min to parallel changes in sexual behavior frequencies. These new controls of estrogen action offer a vast array of possibilities for discrete local controls of estrogen action. They also represent a formidable challenge for neuroendocrinologists trying to obtain an integrated view of brain function in relation to behavior. [less ▲]Detailed reference viewed: 44 (5 ULg)