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See detailEstradiol rapidly activates male sexual behavior and affects brain monoamine levels in the quail brain
Cornil, Charlotte ULg; Dalla, C.; Papadopoulou-Daifoti, Z. et al

in Behavioural Brain Research (2006), 166(1), 110-123

Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular effects mediated via non-genomic mechanisms have however been ... [more ▼]

Steroids are generally viewed as transcription factors binding to intracellular receptors and activating gene transcription. Rapid cellular effects mediated via non-genomic mechanisms have however been identified and one report showed that injections of estradiol rapidly stimulate chemoinvestigation and mounting behavior in castrated male rats. It is not known whether such effects take place in other species and what are the cellular underlying mechanisms. We show here that a single injection of estradiol (500 wg/kg) rapidly and transiently activates copulatory behavior in castrated male quail pre-treated with a dose of testosterone behaviorally ineffective by itself. The maximal behavioral effect was observed after 15 min. In a second experiment, the brain of all subjects was immediately collected after behavioral tests performed 15 min after injection. The preoptic area-hypothalamus (HPOA), hindbrain, telencephalon and cerebellum were isolated and monoamines measured by HPLC-ED. Estradiol increased levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) and 5-HIAA/serotonin ratios in the telencephalon and hindbrain independently of whether animals had mated or not. Estradiol also affected these measures in HPOA and cerebellum but this effect was correlated with the level of sexual activity so that significant effects of the treatment only appeared when sexual activity was used as a covariate. Interactions between estradiol effects and sexual activity were also observed for dopamine in the HPOA and for serotonin in the hindbrain and cerebellum. Together, these data demonstrate that a single estradiol injection rapidly activates male sexual behavior in quail and that this behavioral effect is correlated with changes in monoaminergic activity. (c) 2005 Elsevier B.V. All rights reserved. [less ▲]

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See detailRapid effects of aromatase inhibition on male reproductive behaviors in Japanese quail
Cornil, Charlotte ULg; Taziaux, Mélanie ULg; Baillien, M. et al

in Hormones & Behavior (2006), 49(1), 45-67

Non-genomic effects of steroid hormones on cell physiology have been reported in the brain. However, relatively little is known about the behavioral significance of these actions. Male sexual behavior is ... [more ▼]

Non-genomic effects of steroid hormones on cell physiology have been reported in the brain. However, relatively little is known about the behavioral significance of these actions. Male sexual behavior is activated by testosterone partly through its conversion to estradiol via the enzyme aromatase in the preoptic area (POA). Brain aromatase activity (AA) changes rapidly which might in turn be important for the rapid regulation of behavior. Here, acute effects of Vorozole (TM), an aromatase inhibitor, injected IP at different doses and times before testing (between 15 and 60 min), were assessed on male sexual behavior in quail. To limit the risk of committing both types of statistical errors (I and II), data of all experiments were entered into a meta-analysis. Vorozole (TM) significantly inhibited mount attempts (P < 0.05, size effect [g] = 0.527) and increased the latency to first copulation (P < 0.05, g = 0.251). The treatment had no effect on the other measures of copulatory behavior. Vorozole (TM) also inhibited appetitive sexual behavior measured by the social proximity response (P < 0.05, g = 0.534) or rhythmic cloacal sphincter movements (P < 0.001, g = 0.408). Behavioral inhibitions always reached a maximum at 30 min. Another aromatase inhibitor, androstatrienedione, induced a similar rapid inhibition of sphincter movements. Radioenzyme assays demonstrated that within 30 min Vorozole (TM) had reached the POA and completely blocked AA measured in homogenates. When added to the extracellular milieu, Vorozole (TM) also blocked within 5 min the AA in POA explants maintained in vitro. Together, these data demonstrate that aromatase inhibition rapidly decreases both consummatory and appetitive aspects of male sexual behavior. (c) 2005 Elsevier Inc. All rights reserved. [less ▲]

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See detailRapid control of brain aromatase activity by glutamatergic inputs
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Endocrinology (2006), 147(1), 359-366

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on ... [more ▼]

Estrogens derived from the neural aromatization of testosterone play a key role in the activation of male sexual behavior in many vertebrates and have now been recognized to have rapid membrane effects on brain function. Such changes in aromatase activity and hence in local estrogen concentrations could rapidly modulate behavioral responses. We show here that there is a very rapid (within minutes) decrease in aromatase activity in quail hypothalamic explants exposed to treatments affecting intracellular Ca2+ concentrations, such as the addition of glutamate agonists (kainate, alpha-amino-3-hydroxymethyl-4-isoxazole propionic acid, and, to a much lesser extent, N-methyl-D-aspartate), but not of gamma-aminobutyric acid. The kainate effects, which reduce aromatase activity by 25-50%, are observed within 5 min, are completely blocked in explants exposed to specific kainate antagonists (6-cyano-7-nitroquinoxaline-2,3-dione disodium or 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide disodium), and are also rapidly reversible when effectors are washed out. Together, these data support the idea that the synthesis of estrogen can be rapidly regulated in the brain, thus producing rapid changes in local estrogen bioavailability that could rapidly modify brain function with a time course similar to what has previously been described for neurotransmitters and neuromodulators. [less ▲]

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See detailRapid changes in production and behavioral action of estrogens.
Balthazart, Jacques ULg; Cornil, Charlotte ULg; Taziaux, Mélanie ULg et al

in Neuroscience (2006), 138(3), 783-91

It is well established that sex steroid hormones bind to nuclear receptors, which then act as transcription factors to control brain sexual differentiation and the activation of sexual behaviors ... [more ▼]

It is well established that sex steroid hormones bind to nuclear receptors, which then act as transcription factors to control brain sexual differentiation and the activation of sexual behaviors. Estrogens locally produced in the brain exert their behavioral effects in this way but mounting evidence indicates that estrogens also can influence brain functioning more rapidly via non-genomic mechanisms. We recently reported that, in Japanese quail, the activity of preoptic estrogen synthase (aromatase) can be modulated quite rapidly (within minutes) by non-genomic mechanisms, including calcium-dependent phosphorylations. Behavioral studies further demonstrated that rapid changes in estrogen bioavailability, resulting either from a single injection of a high dose of estradiol or from the acute inhibition of aromatase activity, significantly affect the expression of both appetitive and consummatory aspects of male sexual behavior with latencies ranging between 15 and 30 min. Together these data indicate that the bioavailability of estrogens in the brain can change on different time-scales (long- and short-term) that match well with the genomic and non-genomic actions of this steroid and underlie two complementary mechanisms through which estrogens modulate behavior. Estrogens produced locally in the brain should therefore be considered not only as neuroactive steroids but they also display many (if not all) functional characteristics of neuromodulators and perhaps neurotransmitters. [less ▲]

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See detailSocially induced and rapid increases in aggression are inversely related to brain aromatase activity in a sex-changing fish, Lythrypnus dalli
Black, M. P.; Balthazart, Jacques ULg; Baillien, M. et al

in Proceedings of the Royal Society B : Biological Sciences (2005), 272(1579), 2435-2440

Social interactions can generate rapid and dramatic changes in behaviour and neuroendocrine activity. We investigated the effects of a changing social environment on aggressive behaviour and brain ... [more ▼]

Social interactions can generate rapid and dramatic changes in behaviour and neuroendocrine activity. We investigated the effects of a changing social environment on aggressive behaviour and brain aromatase activity (bAA) in a sex-changing fish, Lythrypnus dalli. Aromatase is responsible for the conversion of androgen into oestradiol. Male removal from a socially stable group resulted in rapid and dramatic (>= 200%) increases in aggression in the dominant female, which will become male usually 7-10 days later. These dominant females and recently sex-changed individuals had lower bAA but similar gonadal aromatase activity (gAA) compared to control females, while established males had lower bAA than all groups and lower gAA than all groups except dominant females. Within hours of male removal, dominant females' aggressive behaviour was inversely related to bAA but not gAA. These results are novel because they are the first to: (i) demonstrate socially induced decreases in bAA levels corresponding with increased aggression, (ii) identify this process as a possible neurochemical mechanism regulating the induction of behavioural, and subsequently gonadal, sex change and (iii) show differential regulation of bAA versus gAA resulting from social manipulations. Combined with other studies, this suggests that aromatase activity may modulate fast changes in vertebrate social behaviour. [less ▲]

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See detailRapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior
Cornil, Charlotte ULg; Dalla, C.; Papadopoulou-Daifoti, Z. et al

in Endocrinology (2005), 146(9), 3809-3820

In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the ... [more ▼]

In Japanese quail, as in rats, the expression of male sexual behavior over relatively long time periods (days to weeks) is dependent on the local production of estradiol in the preoptic area via the aromatization of testosterone. On a short-term basis (minutes to hours), central actions of dopamine as well as locally produced estrogens modulate behavioral expression. In rats, a view of and sexual interaction with a female increase dopamine release in the preoptic area. In quail, in vitro brain aromatase activity (AA) is rapidly modulated by calcium-dependent phosphorylations that are likely to occur in vivo as a result of changes in neurotransmitter activity. Furthermore, an acute estradiol injection rapidly stimulates copulation in quail, whereas a single injection of the aromatase inhibitor vorozole rapidly inhibits this behavior. We hypothesized that brain aromatase and dopaminergic activities are regulated in quail in association with the expression of male sexual behavior. Visual access as well as sexual interactions with a female produced a significant decrease in brain AA, which was maximal after 5 min. This expression of sexual behavior also resulted in a significant decrease in dopaminergic as well as serotonergic activity after 1 min, which returned to basal levels after 5 min. These results demonstrate for the first time that AA is rapidly modulated in vivo in parallel with changes in dopamine activity. Sexual interactions with the female decreased aromatase and dopamine activities. These data challenge established views about the causal relationships among dopamine, estrogen action, and male sexual behavior. [less ▲]

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See detailInteractions between kinases and phosphatases in the rapid control of brain aromatase
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Journal of Neuroendocrinology (2005), 17(9), 553-559

Aromatization of testosterone into oestradiol plays a key role in the activation of male sexual behaviour in many vertebrate species. Rapid changes in brain aromatase activity have recently been ... [more ▼]

Aromatization of testosterone into oestradiol plays a key role in the activation of male sexual behaviour in many vertebrate species. Rapid changes in brain aromatase activity have recently been identified and the resulting changes in local oestrogen bioavailability could modulate fast behavioural responses to oestrogens. In quail hypothalamic homogenates, aromatase activity is down-regulated within minutes by calcium-dependent phosphorylations in the presence of ATP, MgCl2 and CaCl2 (ATP/Mg/Ca). Three kinases (protein kinases A and C and calmodulin kinase; PKA, PKC and CAMK) are potentially implicated in this process. If kinases decrease aromatase activity in a reversible manner, then it would be expected that the enzymatic activity would increase and/or return to baseline levels in the presence of phosphatases. We showed previously that 0.1 mM vanadate (a general inhibitor of protein phosphatases) significantly decreases aromatase activity but specific protein phosphatases that could up-regulate aromatase activity have not been identified to date. The reversibility of aromatase activity inhibition by phosphorylations was investigated in the present study using alkaline and acid phosphatase (Alk and Ac PPase). Unexpectedly, Alk PPase inhibited aromatase activity in a dose-dependent manner in the presence, as well as in the absence, of ATP/Mg/Ca. By contrast, Ac PPase completely blocked the inhibitory effects of ATP/Mg/Ca on aromatase activity, even if it moderately inhibited aromatase activity in the absence of ATP/Mg/Ca. However, the addition of Ac PPase was unable to restore aromatase activity after it had been inhibited by exposure to ATP/Mg/Ca. Taken together, these data suggest that, amongst the 15 potential consensus phosphorylation sites identified on the quail aromatase sequence, some must be constitutively phosphorylated for the enzyme to be active whereas phosphorylation of the others is involved in the rapid inhibition of aromatase activity by the competitive effects of protein kinases and phosphatases. Two out of these 15 putative phosphorylation sites occur in an environment corresponding to the consensus sites for PKC, PKA (and possibly a CAMK) and, in all probability, represent the sites whose phosphorylation rapidly blocks enzyme activity. [less ▲]

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See detailEffects of calmodulin on aromatase activity in the preoptic area.
Balthazart, Jacques ULg; Baillien, M.; Charlier, Thierry ULg et al

in Journal of Neuroendocrinology (2005), 17(10), 664-71

Oestrogens derived from the neural aromatisation of testosterone play a key role in the activation of male sexual behaviour in many vertebrates. Besides their slow action on gene transcription mediated by ... [more ▼]

Oestrogens derived from the neural aromatisation of testosterone play a key role in the activation of male sexual behaviour in many vertebrates. Besides their slow action on gene transcription mediated by the binding to nuclear receptors, oestrogens have now been recognised to have more rapid membrane-based effects on brain function. Rapid changes in aromatase activity, and hence in local oestrogen concentrations, could thus rapidly modulate behavioural responses. We previously demonstrated that calcium-dependent kinases are able to down-regulate aromatase activity after incubations of 10-15 min in phosphorylating conditions. In the present study, in quail hypothalamic homogenates, we show that Ca2+ or calmodulin alone can very rapidly change aromatase activity. Preincubation with 1 mM EGTA or with a monoclonal antibody raised against calmodulin immediately increased aromatase activity. The presence of calmodulin on aromatase purified by immunoprecipitation and electrophoresis was previously identified by western blot and two consensus binding sites for Ca2+-calmodulin are identified here on the deduced amino acid sequence of the quail brain aromatase. The rapid control of brain aromatase activity thus appears to include two mechanisms: (i) an immediate regulatory process that involves the Ca2+-calmodulin binding site and (ii) a somewhat slower phosphorylation by several protein kinases (PKC, PKA but also possibly Ca2+-calmodulin kinases) of the aromatase molecule. [less ▲]

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See detailPreoptic aromatase modulates male sexual behavior: slow and fast mechanisms of action
Balthazart, Jacques ULg; Baillien, M.; Cornil, Charlotte ULg et al

in Physiology & Behavior (2004), 83(2), 247-270

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by ... [more ▼]

In many species, copulatory behavior and appetitive (anticipatory/motivational) aspects of male sexual behavior are activated by the action in the preoptic area of estrogens locally produced by testosterone aromatization. Estrogens bind to intracellular receptors, which then act as transcription factors to activate the behavior. Accordingly, changes in aromatase activity (AA) result from slow steroid-induced modifications of enzyme transcription. More recently, rapid nongenomic effects of estrogens have been described and evidence has accumulated indicating that AA can be modulated by rapid (minutes to hour) nongenomic mechanisms in addition to the slower transcriptional changes. Hypothalamic AA is rapidly down-regulated in conditions that enhance protein phosphorylation, in particular, increases in the intracellular calcium concentration, such as those triggered by neurotransmitter (e.g., glutamate) activity. Fast changes in brain estrogens can thus be caused by aromatase phosphorylation as a result of changes in neurotransmission. In parallel, recent studies demonstrate that the pharmacological blockade of AA by specific inhibitors rapidly (within 15-45 min) down-regulates motivational and consummatory aspects of male sexual behavior in quail while injections of estradiol can rapidly increase the expression of copulatory behavior. These data collectively support an emerging concept in neuroendocrinology, namely that estrogen, locally produced in the brain, regulates male sexual behavior via a combination of genomic and nongenomic mechanisms. Rapid and slower changes of brain AA match well with these two modes of estrogen action and provide temporal variations in the estrogen's bioavailability that can support the entire range of established effects for this steroid. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailRapid regulation of brain aromatase activity by afferent inputs: Behavioral implications
Balthazart, Jacques ULg; Baillien, M.; Cornil, Charlotte ULg

in Hormones & Behavior (2004, June), 46(1), 127

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See detailRapid and correlated changes in brain aromatase activity and aggressive behavior are socially-mediated in Lythrypnus dalli
Black, M.; Balthazart, Jacques ULg; Baillien, M. et al

in Hormones & Behavior (2004, June), 46(1), 107-108

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See detailRelationships between aromatase activity in the brain and gonads and behavioural deficits in homozygous and heterozygous aromatase knockout mice
Bakker, Julie ULg; Baillien, M.; Honda, S. et al

in Journal of Neuroendocrinology (2004), 16(5), 483-490

The present study was carried out to determine whether aromatase knockout (ArKO) mice are completely devoid of aromatase activity in their brain and gonads and to compare aromatase activity in wild-type ... [more ▼]

The present study was carried out to determine whether aromatase knockout (ArKO) mice are completely devoid of aromatase activity in their brain and gonads and to compare aromatase activity in wild-type and ArKO mice, as well as in heterozygous (HET) mice of both sexes that were previously shown to display a variety of reproductive behaviours; at levels intermediate between wild-type and ArKO mice. Aromatase activity was extremely low, and undetectable by the tritiated water assay, in homogenates of the preoptic area-hypothalamus of adult wild-type mice, but was induced following a 12-day treatment with testosterone. The induction of aromatase activity by testosterone was significantly larger in males than in females. Even after 12 days exposure to testosterone, no aromatase activity was detected in the brain of ArKO mice of either sex whereas HET mice showed intermediate levels of activity between ArKO and wild-type. Aromatase activity was also undetectable in the ovary of adult ArKO females but was very high in the wildtype ovary and intermediate in the HET ovary. In wild-type mice, a high level of aromatase activity was detected on the day of birth even without pretreatment with testosterone. This neonatal activity was higher in males than in females, but females nevertheless appear to display a substantial level of oestrogen production in their brain. Aromatase activity was undetectable in the brain of newborn ArKO males and females and was intermediate between wild-type and ArKO in HET mice. In conclusion, the present study confirms that ArKO mice are unable to synthesize any oestrogens, thereby validating the ArKO mouse as a valuable tool in the study of the physiological roles of oestradiol. In addition, it demonstrates that the intermediate behaviour of HET mice presumably reflects the effect of gene dosage on aromatase expression and activity, that aromatase activity is sexually differentiated in mice during the neonatal period as well as in adulthood and, finally, that the neonatal female brain produces substantial amounts of oestrogens that could play a significant role in the sexual differentiation of the female brain early in life. [less ▲]

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See detailTerritorial aggression, circulating levels of testosterone, and brain aromatase activity in free-living pied flycatchers
Silverin, B.; Baillien, M.; Balthazart, Jacques ULg

in Hormones & Behavior (2004), 45(4), 225-234

Testosterone (T) is a critical endocrine factor for the activation of many aspects of reproductive behavior in vertebrates. Castration completely eliminates the display of aggressive and sexual behaviors ... [more ▼]

Testosterone (T) is a critical endocrine factor for the activation of many aspects of reproductive behavior in vertebrates. Castration completely eliminates the display of aggressive and sexual behaviors that are restored to intact level by a treatment with exogenous T. There is usually a tight correlation between the temporal changes in plasma T and the frequency of reproductive behaviors during the annual cycle. In contrast, individual levels of behavioral activity are often not related to plasma T concentration at the peak of the reproductive season suggesting that T is available in quantities larger than necessary to activate behavior and that other factors limit the expression of behavior. There is some indication from work in rodents that individual levels of brain aromatase activity (AA) may be a key factor that limits the expression of aggressive behavior, and in agreement with this idea, many studies indicate that estrogens produced in the brain by the aromatization of T may contribute to the activation of reproductive behavior, including aggression. We investigated here in pied flycatcher (Ficedula hypoleuca) the relationships among territorial aggression, plasma T, and brain AA at the peak of the reproductive season. In a first experiment, blood samples were collected from impaired males holding a primary territory and, I or 2 days later, their aggressive behavior was quantified during standardized simulated territorial intrusions. No relationship was found between individual differences in aggressive behavior and plasma T or dihydrotestosterone levels but a significant negative correlation was observed between number of attacks and plasma corticosterone. In a second experiment, aggressive behavior was measured during a simulated territorial intrusion in 22 impaired males holding primary territories. They were then immediately captured and AA was measured in their anterior and posterior diencephalon and in the entire telencephalon. Five males that had attracted a female (who had started egg-laying) were also studied. The paired males were less aggressive and correlatively had a lower AA in the anterior diencephalon but not in the posterior diencephalon and telencephalon than the 22 birds holding a territory before arrival of a female. In these 22 birds, a significant correlation was observed between number of attacks/min displayed during the simulated territorial intrusion and AA in the anterior diencephalon but no correlation was found between these variables in the two other brain areas. Taken together, these data indicate that the level of aggression displayed by males defending their primary territory may be limited by the activity of the preoptic aromatase, but plasma T is not playing an important role in establishing individual differences in aggression. Alternatively, it is also possible that brain AA is rapidly affected by agonistic interactions and additional work should be carried out to determine whether the correlation observed between brain AA and aggressive behavior is the result of an effect of the enzyme on behavior or vice versa. In any case, the present data show that preoptic AA can change quite rapidly during the reproductive cycle (within a few days after arrival of the female) indicating that this enzymatic activity is able to regulate rapid behavioral transitions during the reproductive cycle in this species. (C) 2004 Elsevier Inc. All rights reserved. [less ▲]

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See detailInteractions between aromatase (estrogen synthase) and dopamine in the control of male sexual behavior in quail
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Comparative Biochemistry & Physiology Part B (2002), 132(1), 37-55

In male quail, like in other vertebrates including rodents, testosterone acting especially through its estrogenic metabolites is necessary for the activation of male sexual behavior. Also, the ... [more ▼]

In male quail, like in other vertebrates including rodents, testosterone acting especially through its estrogenic metabolites is necessary for the activation of male sexual behavior. Also, the administration of dopamine agonists and antagonists profoundly influences male sexual behavior. How the steroid-sensitive neural network and dopamine interact physiologically, remains largely unknown. It is often implicitly assumed that testosterone or its metabolite estradiol, stimulates male sexual behavior via the modification of dopaminergic transmission. We have now identified in quail two possible ways in which dopamine could potentially affect sexual behavior by modulating the aromatization of testosterone into an estrogen. One is a long-acting mechanism that presumably involves the modification of dopaminergic transmission followed by the alteration of the genomic expression of aromatase. The other is a more rapid mechanism that does not appear to be dopamine receptor-mediated and may involve a direct interaction of dopamine with aromatase (possibly via substrate competition). We review here the experimental data supporting the existence of these controls of aromatase activity by dopamine and discuss the possible contribution of these controls to the activation of male sexual behavior. (C) 2002 Elsevier Science Inc. All rights reserved. [less ▲]

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See detailPhosphorylation processes mediate rapid changes of brain aromatase activity
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Journal of Steroid Biochemistry & Molecular Biology (2001), 79(1-5), 261-277

The enzyme aromatase (also called estrogen synthase) that catalyzes the transformation of testosterone (T) into estradiol plays a key limiting role in the action of T on many aspects of reproduction. The ... [more ▼]

The enzyme aromatase (also called estrogen synthase) that catalyzes the transformation of testosterone (T) into estradiol plays a key limiting role in the action of T on many aspects of reproduction. The distribution and regulation of aromatase in the quail brain has been studied by radioenzyme assays on microdissected brain areas, immunocytochemistry, RT-PCR and in situ hybridization. High levels of aromatase activity (AA) characterize the sexually dimorphic, steroid-sensitive medial preoptic nucleus (PONI), a critical site of T action and aromatization for the activation of male sexual behavior. The boundaries of the POM are clearly outlined by a dense population of aromatase-containing cells as visualized by both immunocytochemistry and in situ hybridization histochemistry. Aromatase synthesis in the POM is controlled by T and its metabolite estradiol, but estradiol receptors alpha (ERalpha) are not normally co-localized with aromatase in this brain area. Estradiol receptor beta (ERbeta) has been recently cloned in quail and localized in POM but we do not yet know whether ERbeta occurs in aromatase cells. It is therefore not known whether estrogens regulate aromatase synthesis directly or by affecting different inputs to aromatase cells as is the case with the gonadotropin releasing hormone neurons. The presence of aromatase in presynaptic boutons suggests that locally formed estrogens may exert part of their effects by non-genomic mechanisms at the membrane level. Rapid effects of estrogens in the brain that presumably take place at the neuronal membrane level have been described in other species. If fast transduction mechanisms for estrogen are available at the membrane level, this will not necessarily result in rapid changes in brain function if the availability of the ligand does not also change rapidly. We demonstrate here that AA in hypothalamic homogenates is rapidly down-regulated by exposure to conditions that enhance protein phosphorylation (addition of Ca2+, Mg2+, ATP). This inhibition is blocked by kinase inhibitors which supports the notion that phosphorylation processes are involved. A rapid (within minutes) and reversible regulation of AA is also observed in hypothalamic explants incubated in vitro and exposed to high Ca2+ levels (K+-induced depolarization, treatment by thapsigargin, by kainate, AMPA or NMDA). The local production and availability of estrogens in the brain can therefore be rapidly changed by Ca2+ based on variation in neurotransmitter activity. Locally-produced estrogens are as a consequence available for non-genomic regulation of neuronal physiology in a manner more akin to the action of a neuropeptide/neurotransmitter than previously thought. (C) 2002 Elsevier Science Ltd. All rights reserved. [less ▲]

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See detailThe control of preoptic aromatase activity by afferent inputs in Japanese quail
Absil, Philippe ULg; Baillien, M.; Ball, G. F. et al

in Brain Research Reviews (2001), 37(1-mars Sp. Iss. SI), 38-58

This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and ... [more ▼]

This review summarizes current knowledge on the mechanisms that control aromatase activity in the quail preoptic area, a brain region that plays a key role in the control of reproduction. Aromatase and aromatase mRNA synthesis in the preoptic area are enhanced by testosterone and its metabolite estradiol, but estradiol receptors of the alpha subtype are not regularly colocalized with aromatase. Estradiol receptors of the beta subtype are present in the preoptic area but it is not yet known whether these receptors are colocalized with aromatase. The regulation by estrogen of aromatase activity may be, in part, trans-synaptically mediated, in a manner that is reminiscent of the ways in which steroids control the activity of gonadotropic hormone releasing hormone neurons, Aromatase-immunoreactive neurons are surrounded by dense networks of vasotocin-immunoreactive and tyrosine hydroxylase-immunoreactive fibers and punctate structures. These inputs are in part steroid-sensitive and could therefore mediate the effects of steroids on aromatase activity. In vivo pharmacological experiments indicate that catecholaminergic depletions significantly affect aromatase activity presumably by modulating aromatase transcription. In addition, in vitro studies on brain homogenates or on preoptic-hypothalamic explants show that aromatase activity can be rapidly modulated by a variety of dopaminergic compounds. These effects do not appear to be mediated by the membrane dopamine receptors and could involve changes in the phosphorylation state of the enzyme, Together, these results provide converging evidence for a direct control of aromatase activity by catecholamines consistent with the anatomical data indicating the presence of a catecholaminergic innervation of aromatase cells. These dopamine-induced changes in aromatase activity are observed after several hours or days and presumably result from changes in aromatase transcription but rapid non-genomic controls have also been identified. The potential significance of these processes for the physiology of reproduction is critically evaluated. (C) 2001 Elsevier Science BY. All rights reserved. [less ▲]

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See detailRapid and Reversible Inhibition of Brain Aromatase Activity
Balthazart, Jacques ULg; Baillien, M.; Ball, G. F.

in Journal of Neuroendocrinology (2001), 13(1), 63-73

Many actions of androgens require their conversion via the enzyme aromatase into oestrogens. Changes in brain aromatase activity are thought to take place via changes in enzyme concentration mediated by ... [more ▼]

Many actions of androgens require their conversion via the enzyme aromatase into oestrogens. Changes in brain aromatase activity are thought to take place via changes in enzyme concentration mediated by effects of sex steroids on aromatase transcription. These changes are relatively slow which fits in well with the fact that oestrogens are generally viewed as slow-acting messengers that act via changes in gene transcription. More recently, fast actions of oestrogens, presumably at the level of the cell membrane, have been described both in the female brain and in the male brain after the conversion of testosterone to oestradiol. It is difficult to reconcile the slow regulation of oestrogen synthesis (that occurs via changes in aromatase concentration) with a rapid action at the membrane level. Even if fast transduction mechanisms are available, this will not result in rapid changes in brain function if the availability of the ligand does not also change rapidly. Here, we report that aromatase activity in neural tissue of male Japanese quail (Coturnix japonica) is rapidly downregulated in the presence of Mg(2+), Ca(2+) and ATP in hypothalamic homogenates and in brain explants exposed to high Ca(2+) levels following a K(+)-induced depolarization or the stimulation of glutamate receptors. The K(+)-induced inhibition of aromatase activity is observed within minutes and reversible. Given that aromatase is present in presynaptic boutons, it is possible that rapidly changing levels of locally produced oestrogen are available for nongenomic regulation of neuronal physiology in a manner more akin to the action of a neuropeptide than previously hypothesized. [less ▲]

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See detailOntogeny of Aromatase and Tyrosine Hydroxylase Activity and of Aromatase-Immunoreactive Cells in the Preoptic Area of Male and Female Japanese Quail
Balthazart, Jacques ULg; Tlemcani, O.; Harada, N. et al

in Journal of Neuroendocrinology (2000), 12(9), 853-66

The aromatization of testosterone into oestrogens plays a key role in the control of many behavioural and physiological aspects of reproduction. In the quail preoptic area (POA), aromatase activity and ... [more ▼]

The aromatization of testosterone into oestrogens plays a key role in the control of many behavioural and physiological aspects of reproduction. In the quail preoptic area (POA), aromatase activity and the number of aromatase-immunoreactive (ARO-ir) cells are sexually differentiated (males > females). This sex difference is implicated in the control of the sexually dimorphic behavioural response of quail to testosterone. We analysed the ontogenetic development of this sex difference by measuring aromatase activity and counting ARO-ir cells in the POA of males and females from day 1 post hatch to sexual maturity. We investigated in parallel another enzyme: tyrosine hydroxylase, the rate limiting step in catecholamine synthesis. Between hatching and 4 weeks of age, aromatase activity levels were low and equal in males and females. Aromatase activity then markedly increased in both sexes when subjects initiated their sexual maturation but this increase was more pronounced in males so that a marked difference in aromatase activity was present in 6 and 8 week-old subjects. Tyrosine hydroxylase activity progressively increased with age starting immediately after hatching and there was no abrupt modification in the slope of this increase when birds became sexually mature. No sex difference was detected in the activity of this enzyme. The number of ARO-ir cells in the POA progressively increased with age starting at hatching. No sex difference in ARO-ir cell numbers could be detected before subjects reached full sexual maturity. The analysis of the three-dimensional organization of ARO-ir cells in the POA revealed that, with increasing ages, ARO-ir cells acquire a progressively more lateral position: they are largely periventricular in young birds but they are found at higher density in the lateral part of the medial preoptic nucleus in adults. These data indicate that aromatase activity differentiates sexually when birds reach sexual maturity presumably under the activating effects of the increased testosterone levels in males. The number of ARO-ir cells, however, begins to increase in a non sexually differentiated manner before the rise in plasma testosterone in parallel with the increased tyrosine hydroxylase activity. Whether this temporal coincidence results from a general ontogenetic pattern or from more direct causal links remains to be established. [less ▲]

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See detailLocalization and Controls of Aromatase in the Quail Spinal Cord
Evrard, H.; Baillien, M.; Foidart, Agnès ULg et al

in Journal of Comparative Neurology (The) (2000), 423(4), 552-64

In adult male and female Japanese quail, aromatase-immunoreactive cells were identified in the spinal dorsal horns from the upper cervical segments to the lower caudal area. These immunoreactive cells are ... [more ▼]

In adult male and female Japanese quail, aromatase-immunoreactive cells were identified in the spinal dorsal horns from the upper cervical segments to the lower caudal area. These immunoreactive cells are located mostly in laminae I-III, with additional sparse cells being present in the medial part of lamina V and, at the cervical level exclusively, in lamina X around the central canal. Radioenzyme assays based on the measurement of tritiated water release confirmed the presence of substantial levels of aromatase activity throughout the rostrocaudal extent of the spinal cord. Contrary to what is observed in the brain, this enzyme activity and the number of aromatase-immunoreactive cells in five representative segments of the spinal cord are not different in sexually mature males or females and are not influenced in males by castration with or without testosterone treatment. The aromatase activity and the numbers of aromatase-immunoreactive cells per section are higher at the brachial and thoracic levels than in the cervical and lumbar segments. These experiments demonstrate for the first time the presence of local estrogen production in the spinal cord of a higher vertebrate. This production was localized in the sensory fields of the dorsal horn, where estrogen receptors have been identified previously in several avian and mammalian species, suggesting an implication of aromatase in the modulation of sensory (particularly nociceptive) processes. [less ▲]

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See detailRegional Distribution and Control of Tyrosine Hydroxylase Activity in the Quail Brain
Baillien, M.; Foidart, Agnès ULg; Balthazart, Jacques ULg

in Brain Research Bulletin (1999), 48(1), 3-17

Tyrosine hydroxylase (TH) activity, the rate-limiting step in the synthesis of catecholamines, was quantified in the preoptic area-hypothalamus of adult male Japanese quail by a new assay measuring the ... [more ▼]

Tyrosine hydroxylase (TH) activity, the rate-limiting step in the synthesis of catecholamines, was quantified in the preoptic area-hypothalamus of adult male Japanese quail by a new assay measuring the tritiated water production from 3,5-[3H]-L-tyrosine. Maximal levels of activity were observed at a 20-25 microM concentration of substrate, with more than 50% inhibition of the activity being recorded at a 100 microM concentration. TH activity was linear as a function of the incubation time during the first 20 min and maximal at a pH of 6.0. TH was heterogeneously distributed in the quail brain with highest levels of activity being found (in decreasing order) in the mesencephalon, diencephalon, and telencephalon. Given the large size of the telencephalon, this is the brain area that contains, as a whole, the highest level of enzyme activity. TH inhibitors that have been well-characterized in mammals, such as 3-iodo-L-tyrosine and L-alpha-methyl-p-tyrosine (AMPT) completely inhibited the enzyme activity at a 100 microM concentration. In mammals, the accumulation of catecholamines exerts a negative feedback control on TH activity. Similar controls were observed in the quail brain. Two inhibitors of the DOPA decarboxylase that should lead to accumulation of DOPA depressed TH activity by 60% or more, and the inhibitor of the dopamine beta-hydroxylase, fusaric acid that should cause an accumulation of dopamine, suppressed 90% of the TH activity. The addition of exogenous DOPA, dopamine, or norepinephrine to the brain homogenates also strongly inhibited TH activity, independently confirming the feedback effects of the enzyme products on the enzyme activity. These data demonstrate that TH activity in the quail brain is heterogeneously distributed and acutely regulated, as it is in mammals, by the accumulation of its products and of the derived catecholamines. [less ▲]

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