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See detailDifferential effects of testosterone on protein synthesis activity in male and female quail brain
Dermon, C. R.; Stamatakis, A.; Giakoumaki, S. et al

in Neuroscience (2004), 123(3), 647-666

In Japanese quail, testosterone (T) increases the Nissl staining density in the medial preoptic nucleus (POM) in relation to the differential activation by T of copulatory behavior. The effect of T on ... [more ▼]

In Japanese quail, testosterone (T) increases the Nissl staining density in the medial preoptic nucleus (POM) in relation to the differential activation by T of copulatory behavior. The effect of T on protein synthesis was quantified here in 97 discrete brain regions by the in vivo autoradio-graphic C-14-leucine (Leu) incorporation method in adult gonadectomized male and female quail that had been treated for 4 weeks with T or left without hormone. T activated male sexual behaviors in males but not females. Overall Leu incorporation was increased by T in five brain regions, many of which contain sex steroid receptors such as the POM, archistriatum and lateral hypothalamus. T decreased Leu incorporation in the medial septum. Leu incorporation was higher in males than females in two nuclei but higher in females in three nuclei including the hypothalamic ventromedial nucleus. Significant interactions between effects of T and sex were seen in 13 nuclei: in most nuclei (n=12), T increased Leu incorporation in males but decreased it in females. The POM boundaries were defined by a denser Leu incorporation than the surrounding area and incorporation was increased by T more in males (25%) than in females (15%). These results confirm that protein synthesis in brain areas relevant to the control of sexual behavior can be affected by the sex of the subjects or their endocrine condition and that T can have differential effects in the two sexes. These anabolic changes should reflect the sexually differentiated neurochemical mechanisms mediating behavioral activation. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. [less ▲]

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See detailThe aromatase knockout (ArKO) mouse provides new evidence that estrogens are required for the development of the female brain
Bakker, Julie ULg; Honda, S.; Harada, N. et al

in Annals of the New York Academy of Sciences (2003), 1007

The classic view of sexual differentiation is that the male brain develops under the influence of testicular secretions, whereas the female brain develops in the absence of any hormonal stimulation ... [more ▼]

The classic view of sexual differentiation is that the male brain develops under the influence of testicular secretions, whereas the female brain develops in the absence of any hormonal stimulation. However, several studies have suggested a possible role of estradiol in female neural development, although they did not provide unequivocal evidence that estradiol is indispensable for the development of the female brain and behavior. As a result, the hypothesis subsequently languished because of the lack of a suitable animal model to test estrogen's possible contribution to female differentiation. The recent introduction of the aromatase knockout (ArKO) mouse, which is deficient in aromatase activity because of a targeted mutation in the CYP19 gene and therefore cannot aromatize androgen to estrogen, has provided a new opportunity to reopen the debate of whether estradiol contributes to the development of the female brain. Female ArKO mice showed reduced levels of lordosis behavior after adult treatment with estradiol and progesterone, suggesting that estradiol is required for the development of the neural mechanisms controlling this behavior in female mice. The neural systems affected may include the olfactory systems in that ArKO females also showed impairments in olfactory investigation of odors from conspecifics. Thus, the classic view of sexual differentiation, that is, the female brain develops in the absence of any hormonal secretion, needs to be re-examined. [less ▲]

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See detailIn vivo dynamic ME-MRI reveals differential functional responses of RA- and area X-projecting neurons in the HVC of canaries exposed to conspecific song
Tindemans, I.; Verhoye, M.; Balthazart, Jacques ULg et al

in European Journal of Neuroscience (2003), 18(12), 3352-3360

HVC (nidopallial area, formerly known as hyperstriatum ventrale pars caudalis), a key centre for song control in oscines, responds in a selective manner to conspecific songs as indicated by ... [more ▼]

HVC (nidopallial area, formerly known as hyperstriatum ventrale pars caudalis), a key centre for song control in oscines, responds in a selective manner to conspecific songs as indicated by electrophysiology. However, immediate-early gene induction cannot be detected in this nucleus following song stimulation. HVC contains neurons projecting either towards the nucleus robustus archistriatalis (RA; motor pathway) or area X (anterior forebrain pathway). Both RA- and area X-projecting cells show auditory responses. The present study analysed these responses separately in the two types of HVC projection neurons of canaries by a new in vivo approach using manganese as a calcium analogue which can be transported anterogradely and used as a paramagnetic contrast agent for magnetic resonance imaging (MRI). Manganese was stereotaxically injected into HVC and taken up by HVC neurons. The anterograde axonal transport of manganese from HVC to RA and area X was then followed by MRI during approximate to 8 h and changes in signal intensity in these targets were fitted to sigmoid functions. Data comparing birds exposed or not to conspecific songs revealed that song stimulation specifically affected the activity of the two types of HVC projection neurons (increase in the sigmoid slope in RA and in its maximum signal intensity in area X). Dynamic manganese-enhanced MRI thus allows assessment of the functional state of specific neuronal populations in the song system of living canaries in a manner reminiscent of functional MRI (but with higher resolution) or of 2-deoxyglucose autoradiography (but in living subjects). [less ▲]

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See detailAromatase (estrogen synthase) activity in the dorsal horn of the spinal cord: Functional implications
Evrard, H. C.; Balthazart, Jacques ULg

in Annals of the New York Academy of Sciences (2003), 1007

The presence of aromatase (estrogen synthase) in neurons in the dorsal horn of the spinal cord in Japanese quail suggests that estrogens produced locally from androgens could control spinal sensory ... [more ▼]

The presence of aromatase (estrogen synthase) in neurons in the dorsal horn of the spinal cord in Japanese quail suggests that estrogens produced locally from androgens could control spinal sensory processes including nociception. We used the hot water nociceptive test (54 degreesC) to appraise the longterm effect of an inhibition of aromatization on the foot withdrawal latency in male quail. Four weeks after the ablation of their main source of testosterone (testes), castrated males displayed a significantly higher foot withdrawal latency than gonadally intact males. A prolonged treatment with subcutaneous capsules filled with testosterone or 17 beta-estradiol restored the baseline latency within 2 weeks. The effect of testosterone in castrated quail was almost completely blocked by systemic injections of Vorozole((TM)), a nonsteroidal aromatase inhibitor or tamoxifen, an estrogen receptor antagonist (one injection per day for 10 days). Taken together, these data demonstrate for the first time to our knowledge an effect of estrogens formed by aromatization of androgens on nociception. Because aromatase-immunoreactive neurons and aromatase activity are present in the dorsal horns of the spinal cord, this control of pain thresholds is presumably mediated, at least in part, by estrogens produced at the spinal level that act locally via slow, presumably genomic, mechanisms mediated by the activation of spinal nuclear estrogen receptors. [less ▲]

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See detailSpecific innervation of aromatase neurons by substance P fibers in the dorsal horn of the spinal cord in quail
Evrard, H. C.; Willems, Evelyne ULg; Harada, N. et al

in Journal of Comparative Neurology (2003), 465(2), 309-318

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in ... [more ▼]

The enzyme aromatase catalyzes the production of estrogens in the dorsal horn of the spinal cord where most of the nociceptive primary afferent fibers terminate. Numerous estrogen receptors are present in this area and the control of spinal aromatase activity is thought to play an important role in the estrogenic control of nociception. The coexistence of aromatase and nociceptive terminals suggests a role for aromatase cells in pain-related processes, but whether terminals releasing nociceptive neuropeptides (e.g., substance P) actually contact aromatase neurons is unknown and the factors that control spinal aromatase activity have not yet been identified. In the present study we analyzed by double-label immunocytochemistry the distribution in the Japanese quail spinal cord, of aromatase and of substance P or its receptor (neurokinin 1 receptor). All antigens were mainly localized in laminae I and II as observed in mammals. Most aromatase neurons were colocalized with neurokinin 1 receptors and were in close apposition with substance P-immunoreactive fibers. These results suggest that aromatase neurons are responsive to noxious stimulation and may participate in the control of nociception. Furthermore, spinal aromatase activity could be controlled by substance P through a regulation of the aromatase gene transcription as reported for the mouse diencephalon and/or through neurokinin 1 receptor-dependent phosphorylation of the aromatase protein. [less ▲]

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See detailBirds return every spring like clockwork, but where is the clock?
Ball, G. F.; Balthazart, Jacques ULg

in Endocrinology (2003), 144(9), 3739-3741

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See detailEffect of age and testosterone on autumnal neurogenesis in male European starlings (Sturnus vulgaris)
Absil, Philippe ULg; Pinxten, R.; Balthazart, Jacques ULg et al

in Behavioural Brain Research (2003), 143(1), 15-30

The male European starling (Sturnus vulgaris) is an open-ended learner that increases its repertoire throughout life. In parallel, the volume of hi-h vocal center (HVC) is larger in older birds than in ... [more ▼]

The male European starling (Sturnus vulgaris) is an open-ended learner that increases its repertoire throughout life. In parallel, the volume of hi-h vocal center (HVC) is larger in older birds than in yearlings. We labeled with the thymidine analog 5-bromodeoxyuridine (BrdU) the cells that are generated during the fall in the brain of adult males that were 2 or more years old and in yearling males that were treated with exogenous testosterone (T) or kept intact before BrdU administration. In all subjects, the singing rate was recorded and BrdU-Iabeled cells were quantified in HVC, in proliferative areas of the ventricular zone (VZ) and in auditory regions. BrdU-containing cells were observed in all brain regions investigated. They were significantly more numerous in the VZ of the T-treated yearlings than in any other group. In older birds, a reduced number of labeled cells was specifically observed in the VZ close to the anterior commissure. No group difference was detected in auditory processing areas or in HVC. These data show for the first time a positive influence of T on the production of new cells at the VZ level in a male songbird and a decrease of this process with age. Furthermore, in T-treated birds, a correlation was observed between the HVC volume and the number of differentiated (round) BrdU-positive cell numbers in HVC on the one hand and song rate on another hand supporting the notion that singing activity is causally related to the T-induced growth of this song control nucleus. (C) 2003 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailCalcium-dependent phosphorylation processes control brain aromatase in quail
Balthazart, Jacques ULg; Baillien, Michelle; Charlier, Thierry ULg et al

in European Journal of Neuroscience (2003), 17(8), 1591-1606

Increased gene transcription activated by the binding of sex steroids to their cognate receptors is one important way in which oestrogen synthase (aromatase) activity is regulated in the brain. This ... [more ▼]

Increased gene transcription activated by the binding of sex steroids to their cognate receptors is one important way in which oestrogen synthase (aromatase) activity is regulated in the brain. This control mechanism is relatively slow (hours to days) but recent data indicate that aromatase activity in quail preoptic-hypothalamic homogenates is also rapidly (within minutes) affected by exposure to conditions that enhance Ca2+-dependent protein phosphorylation. We demonstrate here that Ca2+-dependent phosphorylations controlled by the activity of multiple protein kinases including PKC, and possibly also PKA and CAMK, can rapidly down-regulate aromatase activity in brain homogenates. These phosphorylations directly affect the aromatase molecule itself. Western blotting experiments on aromatase purified by immunoprecipitation reveal the presence on the enzyme of phosphorylated serine, threonine and tyrosine residues in concentrations that are increased by phosphorylating conditions. Cloning and sequencing of the quail aromatase identified a 1541-bp open reading frame that encodes a predicted 490-amino-acid protein containing all the functional domains that have been previously described in the mammalian and avian aromatase. Fifteen predicted consensus phosphorylation sites were identified in this sequence, but only two of these (threonine 455 and 486) match the consensus sequences corresponding to the protein kinases that were shown to affect aromatase activity during the pharmacological experiments (i.e. PKC and PKA). This suggests that the phosphorylation of one or both of these residues represents the mechanism underlying, at least in part, the rapid changes in aromatase activity. [less ▲]

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See detailEffects of testosterone on Reelin expression in the brain of male European starlings
Absil, Philippe ULg; Pinxten, R.; Balthazart, Jacques ULg et al

in Cell & Tissue Research (2003), 312(1), 81-93

Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. We studied the expression of Reelin in the brain of adult ... [more ▼]

Reelin, a large glycoprotein defective in reeler mice, is assumed to determine the final location of migrating neurons in the developing brain. We studied the expression of Reelin in the brain of adult male European starlings that had been treated or not with exogenous testosterone. Reelin-immunoreactive cells and fibers were widely distributed in the forebrain including areas in and around the song control nucleus, HVC. No labeling was detected in other song control nuclei with the exception of nucleus uvaeformis, which was delineated by a dense cluster of Reelin-immunoreactive perikarya. Reelin is thus expressed in areas incorporating new neurons in adulthood, such as HVC. Reelin expression was sharply decreased by testosterone in HVC, nucleus uvaeformis and dorsal thalamus but not in other brain regions. These results are consistent with the idea that seasonal changes in Reelin expression modulate the incorporation of neurons within HVC. The presence of Reelin in other brain areas that do not incorporate new neurons in adulthood indicates, however, that this protein must play other unrelated roles in the adult brain. Additional studies should now be carried out to determine the specific role played by this protein in the seasonal plasticity of the songbird brain. [less ▲]

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See detailSex differences in the distribution of the steroid receptor coactivator SRC-1 in the song control nuclei of male and female canaries
Charlier, Thierry ULg; Balthazart, Jacques ULg; Ball, Gregory F

in Brain Research (2003), 959(2), 263-274

The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. The distribution of SRC-1 transcripts was ... [more ▼]

The steroid receptor coactivator SRC-1 modulates ligand-dependent transactivation of several nuclear receptors, including the receptors for sex steroid hormones. The distribution of SRC-1 transcripts was analyzed here by in situ hybridization in coronal sections through the brain of male and female canaries. A broad but heterogeneous distribution of SRC-1 transcripts was observed with high numbers of densely labeled cells being present in many steroid-sensitive areas including the medial preoptic nucleus, several hypothalamic nuclei, five song control nuclei (HVc, the lateral and medial portion of the magnocellular nucleus of the anterior neostriatum, area X and the nucleus uvaeformis) and several catecholaminergic areas (area ventralis of Tsai, substantia nigra, locus coeruleus). The volume of two song control nuclei, HVc and area X were reconstructed based on the boundaries of the cell groups exhibiting a denser SRC-1 expression as compared to the surrounding areas. Sex differences in the expression of SRC-1 were also detected in several song control nuclei. In particular, the volume of HVc based on the high density of SRC-1 expression was significantly larger in males than in females. The effect of steroids on the song control system could be, at least in part, indirect and result from a modulation by steroids of the catecholaminergic inputs to the song control nuclei. The presence of the steroid receptor coactivator SRC-1 in the telencephalic song control nuclei and in the catecholaminergic cell groups that innervate the song system supports the idea that SRC-1 expression could play an active role in the control of singing behavior by modulating estrogen and androgen receptor action at both locations. (C) 2002 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailAnatomical relationships between aromatase-immunoreactive neurons and nitric oxide synthase as evidenced by NOS immunohistochemistry or NADPH diaphorase histochemistry in the quail forebrain
Balthazart, Jacques ULg; Panzica, G. C.; Krohmer, R. W.

in Journal of Chemical Neuroanatomy (2003), 25(1), 39-51

In Japanese quail (Coturnix japonica), previous studies indicated that the distribution of reduced nicotinamide dinucleotide phosphate (NADPH) diaphorase overlaps with steroid-sensitive areas that contain ... [more ▼]

In Japanese quail (Coturnix japonica), previous studies indicated that the distribution of reduced nicotinamide dinucleotide phosphate (NADPH) diaphorase overlaps with steroid-sensitive areas that contain dense populations of aromatase-immunoreactive (ARO-ir) cells. We investigated here the anatomical relationships between aromatase (ARO) and nitric oxide synthase (NOS)containing cells that were visualized both by NOS-immunohistochemistry and NADPH-histochemistry. The distribution of ARO-ir and of NADPH-positive cells in the forebrain observed here matched exactly the distribution previously reported. The distribution of NOS-immunoreactive material in the vicinity of ARO-ir cell groups appeared similar to the distribution of NADPH-positive structures previously identified by histochemistry. The number of NOS-immunoreactive cells was similar to the number of NADPH-positive cells and them were found in the same brain regions. In contrast. few NOS-immunoreactive fibers were observed whereas numerous NADPH-positive fibers and Punctuate structures were present in many areas. Major groups of NOS-immunoreactive/ NADPH-positive neurons were adjacent to the main ARO-ir cell groups, such as the medial preoptic nucleus. the bed nucleus of the stria terminalis and the nucleus ventromedialis hypothalamic. Hove ever. examination of adjacent sections indicated that there is very little overlap between the NOS-immunoreactive and ARO-ir cell populations. This notion got further support by double-labeled sections where no double-labeled cells could be identified. In sections stained simultaneously by histochemistry for NADPH and immunohistochemistry for ARO, many NADPH-positive fibers and punctate structures were closely associated with ARO-ir perikarya. Taken together, the present data indicate that NOS is not or very rarely colocalized with ARO but that NOS inputs are closely associated with ARO-ir cells. Based on previous work in a variety of model systems. it can be hypothesized that these inputs modulate the expression or activity of ARO in the quail brain. (C) 2002 Elsevier Science B.V. All rights reserved. [less ▲]

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See detailModulation of steroid activity by transcription coactivators in songbirds
Charlier, Thierry ULg; Auger, Catherine J; Balthazart, Jacques ULg et al

in Hormones & Behavior (2003), 44

Songbirds have developed a specialized, steroid-dependent telencephalic vocal control system for the production of learned vocalization. Recent progress in the study of the mechanisms by which steroid ... [more ▼]

Songbirds have developed a specialized, steroid-dependent telencephalic vocal control system for the production of learned vocalization. Recent progress in the study of the mechanisms by which steroid receptors act on the eukaryotic genome has highlighted the role of a newly discovered protein family, the Nuclear Receptor Coactivators. More specifically, the CREB-binding protein (CBP) and the Steroid Receptor Coactivator-1 (SRC-1) have been shown to be actively involved in mediating steroid hormone action in the developing rat brain. The distribution of the coactivator SRC-1 was analyzed in canaries by in situ hybridization. A very broad but heterogeneous distribution of the transcript was observed, mainly in steroid-sensitive areas of the hypothalamus, the song control system and several catecholaminergic areas. The presence of SRC-1 in these regions was also confirmed by immunocytochemistry. A similar very high concentration of the coactivator CBP protein was also found in steroid-sensitive areas of the hypothalamus and in the song system. Sex differences in SRC-1 mRNA concentration were detected in HVC and in area X. Moreover, preliminary data obtained independently in starlings (CBP) and in quail (SRC-1) suggest that the expression of coactivators is regulated by steroids as well as by photoperiod. The presence of these steroid receptor coactivators in the telencephalic song control nuclei and in catecholaminergic cell groups that innervate the song system and their possible regulation by photoperiod and/or steroids support the idea that SRC-1 and CBP could play an important role in the control of singing behavior by modulating estrogen and androgen receptor action. [less ▲]

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See detailCloning and identification of functional domains in quail Brain aromatase
Charlier, Thierry ULg; Baillien, Michelle; Ball, Gregory F. et al

Poster (2003)

Recent evidence indicates that aromatase activity (AA) in the hypothalamus is not only modulated by slow (hours to days) genomic actions but also through fast (seconds to minutes) non-genomic mechanisms ... [more ▼]

Recent evidence indicates that aromatase activity (AA) in the hypothalamus is not only modulated by slow (hours to days) genomic actions but also through fast (seconds to minutes) non-genomic mechanisms. We recently showed that Calcium (Ca2+)-dependent phosphorylations catalyzed by multiple protein kinases including PKC, and possibly PKA and CAMK, rapidly down-regulate AA in quail hypothalamic homogenates. Western blotting experiments also indicated that phosphorylations affect the aromatase molecule itself but it was impossible to fully characterize the putative phosphorylation sites on the quail enzyme because its sequence was unknown. We therefore cloned and sequenced the quail brain aromatase. We identified a 1541-bp open reading frame that encodes a predicted 490-amino acid protein containing all functional domains previously described in mammalian and other avian aromatases. Multiple motifs match consensus sequences corresponding to several protein kinases including those that were shown to affect AA during pharmacological experiments with specific kinase inhibitors (e.g., PKC, PKA, MAPK, Myosine light chain kinase, Tyr. kinase). Another potential control pathway of AA, independent from phosphorylations, could involve a direct control by Ca2+-dependent calmodulin (CAM), as suggested by the identification in Western blots of CAM on purified aromatase from quail hypothalamic homogenates. Accordingly, two Ca2+-dependent calmodulin binding motifs (1-8-14b) as defined by Rhoads and Friedberg (FASEB, 1997, 11:331-340) are present and conserved in most vertebrates including quail aromatase. These results suggest that the phosphorylation of some residues as well as the direct binding of calmodulin on the aromatase protein represent part of the mechanism(s) underlying the rapid changes in AA. [less ▲]

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See detailThe activation of birdsong by testosterone - Multiple sites of action and role of ascending catecholamine projections
Ball, G. F.; Castelino, C. B.; Maney, D. L. et al

in Annals of the New York Academy of Sciences (2003), 1007

Birdsong is a species-typical stereotypic vocalization produced in the context of reproduction and aggression. Among temperate-zone songbirds, it is produced primarily by males, and its frequency and ... [more ▼]

Birdsong is a species-typical stereotypic vocalization produced in the context of reproduction and aggression. Among temperate-zone songbirds, it is produced primarily by males, and its frequency and quality are enhanced by the presence of the gonadal steroid hormone testosterone in the plasma. In the brain, the effects of testosterone on song behavior involve both estrogenic and androgenic metabolites of testosterone that are locally produced and act via their cognate receptors. Androgen, and in some cases estrogen, receptors are present in many specialized forebrain song control nuclei. Testosterone can regulate catecholamine steady-state levels and turnover in these song control regions. Tracing studies combined with immunocytochemistry for tyrosine hydroxylase (a marker of catecholamine synthesis) reveal several catecholamine cell groups that project to forebrain song control nuclei. These brain areas also express the mRNA for either androgen receptors or estrogen receptor alpha, and androgens enhance the expression of tyrosine hydroxylase. Dopaminergic cell groups that project to song nuclei express the protein product of the immediate early gene fos in association with the production of territorial song. Thus, testosterone may be acting on song behavior via these ascending catecholamine cell groups. Chemical lesioning studies suggest that noradrenergic projections to the song system are involved in the latency to produce song and the ability to discriminate conspecific from heterospecific song. The song control circuit may thus be modulated in significant ways via the androgen regulation of forebrain catecholamine systems. [less ▲]

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See detailSong activation by testosterone is associated with an increased catecholaminergic innervation of the song control system in female canaries
Appeltants, D.; Ball, G. F.; Balthazart, Jacques ULg

in Neuroscience (2003), 121(3), 801-814

In canaries, singing and a large number of morphological features of the neural system that mediates the learning, perception and production of song exhibit marked sex differences. Although these ... [more ▼]

In canaries, singing and a large number of morphological features of the neural system that mediates the learning, perception and production of song exhibit marked sex differences. Although these differences have been mainly attributed to sex-specific patterns of the action of testosterone and its metabolites, the mechanisms by which sex steroids regulate brain and behavior are far from being completely understood. Given that the density of immunoreactive catecholaminergic fibers that innervate telencephalic song nuclei in canaries is higher in males, which sing, than in females, which usually do not sing, we hypothesized that some of the effects induced by testosterone on song behavior are mediated through the action of the steroid on the catecholaminergic neurons which innervate the song control nuclei. Therefore, we investigated in female canaries the effects of a treatment with exogenous testosterone on song production, on the volume of song control nuclei, and on the catecholaminergic innervation of these nuclei as assessed by immunocytochemical visualization of tyrosine hydroxylase. Testosterone induced male-like singing in all females and increased by about 80% the volume of two telencephalic song control nuclei, the high vocal center (HVC) and the nucleus robustus archistriatalis (RA). Testosterone also significantly increased the fractional area covered by tyrosine hydroxylase-immunoreactive structures (fibers and varicosities) in most telencephalic song control nuclei (HVC, the lateral and medial parts of the magnocellular nucleus of the anterior neostriatum, the nucleus interfacialis, and to a lesser extent RA). By contrast, testosterone did not affect the catecholaminergic innervation of the telencephalic areas adjacent to HVC and RA. Together these data demonstrate that, in parallel to its effects on song behavior and on the morphology of the song control system, testosterone also regulates the catecholaminergic innervation of most telencephalic song control nuclei in canaries. The endocrine regulation of singing may thus involve the neuromodulatory action of specialized dopaminergic and/or noradrenergic projections onto several key parts of the song control system. (C) 2003 IBRO. Published by Elsevier Ltd. All rights reserved. [less ▲]

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See detailMultiple mechanisms control brain aromatase activity at the genomic and non-genomic level
Balthazart, Jacques ULg; Baillien, Michelle; Charlier, Thierry ULg et al

in Journal of Steroid Biochemistry & Molecular Biology (2003), 86

Evidence has recently accumulated indicating that aromatase activity in the preoptic area is modulated in parallel by both slow (hours to days) genomic and rapid (minutes to hours) non-genomic mechanisms ... [more ▼]

Evidence has recently accumulated indicating that aromatase activity in the preoptic area is modulated in parallel by both slow (hours to days) genomic and rapid (minutes to hours) non-genomic mechanisms. We review here these two types of control mechanisms and their potential contribution to various aspects of brain physiology in quail. High levels of aromatase mRNA, protein and activity (AA) are present in the preoptic area of this species where the transcription of aromatase is controlled mainly by steroids. Estrogens acting in synergy with androgens play a key role in this control and both androgen and estrogen receptors (ER; alpha and beta subtypes) are present in the preoptic area even if they are not necessarily co-localized in the same cells as aromatase. Steroids have more pronounced effects on aromatase transcription in males than in females and this sex difference could be caused, in part, by a sexually differentiated expression of the steroid receptor coactivator 1 in this area. The changes in aromatase concentration presumably control seasonal variations as well as sex differences in brain estrogen production. Aromatase activity in hypothalamic homogenates is also rapidly (within minutes) down-regulated by exposure to conditions that enhance protein phosphorylation such as the presence of high concentrations of calcium, magnesium and ATP. Similarly, pharmacological manipulations such as treatment with thapsigargin or stimulation of various neurotransmitter receptors (alpha-amino-3-hydroxy-methyl-4-isoxazole propionic acid (AMPA), kainate, and N-methyl-d-aspartate (NMDA)) leading to enhanced intracellular calcium concentrations depress within minutes the aromatase activity measured in quail preoptic explants. The effects of receptor stimulation are presumably direct: electrophysiological data confirm the presence of these receptors in the membrane of aromatase-expressing cells. Inhibitors of protein kinases interfere with these processes andWestern blotting experiments on brain aromatase purified by immunoprecipitation confirm that the phosphorylations regulating aromatase activity directly affect the enzyme rather than another regulatory protein. Accordingly, several phosphorylation consensus sites are present on the deduced amino acid sequence of the recently cloned quail aromatase. Fast changes in the local availability of estrogens in the brain can thus be caused by aromatase phosphorylation so that estrogen could rapidly regulate neuronal physiology and behavior. The rapid as well as slower processes of local estrogen production in the brain thus match well with the genomic and non-genomic actions of steroids in the brain. These two processes potentially provide sufficient temporal variation in the bio-availability of estrogens to support the entire range of established effects for this steroid. [less ▲]

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See detailThe neuroendocrinology of reproductive behavior in Japanese quail
Balthazart, Jacques ULg; Baillien, Michelle; Charlier, Thierry ULg et al

in Domestic Animal Endocrinology (2003), 25

Sex steroid hormones such as testosterone have widespread effects on brain physiology and function but one of their best characterized effects arguably involves the activation of male sexual behavior ... [more ▼]

Sex steroid hormones such as testosterone have widespread effects on brain physiology and function but one of their best characterized effects arguably involves the activation of male sexual behavior. During the past 20 years we have investigated the testosterone control of male sexual behavior in an avian species, the Japanese quail (Coturnix japonica).We briefly reviewhere the main features and advantages of this species relating to the investigation of fundamental questions in the field of behavioral neuroendocrinology, a field that studies inter-relationship among hormones, brain and behavior. Special attention is given to the intracellular metabolism of testosterone, in particular its aromatization into an estrogen, which plays a critical limiting role in the mediation of the behavioral effects of testosterone. Brain aromatase activity is controlled by steroids which increase the transcription of the enzyme, but afferent inputs that affect the intraneuronal concentrations of calcium also appear to have a pronounced effect on the enzyme activity through rapid changes in its phosphorylation status. The physiological significance of these slowgenomic and rapid, presumably non-genomic, changes in brain aromatase activity are also briefly discussed. [less ▲]

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See detailChanges in the arginine-vasopressin immunoreactive systems in male mice lacking a functional aromatase gene
Plumari, L.; Viglietti-Panzica, C.; Allieri, F. et al

in Journal of Neuroendocrinology (2002), 14(12), 971-978

In male rodents, the arginine-vasopressin-immunoreactive (AVP-ir) neurones of the bed nucleus of the stria terminalis (BNST) and medial amygdala are controlled by plasma testosterone levels (decreased ... [more ▼]

In male rodents, the arginine-vasopressin-immunoreactive (AVP-ir) neurones of the bed nucleus of the stria terminalis (BNST) and medial amygdala are controlled by plasma testosterone levels (decreased after castration and restored by exogenous testosterone). AVP transcription in these nuclei is increased in adulthood by a synergistic action of the androgenic and oestrogenic metabolites of testosterone and, accordingly, androgen and oestrogen receptors are present in both BNST and medial amygdala. We used knockout mice lacking a functional aromatase enzyme (ArKO) to investigate the effects of a chronic depletion of oestrogens on the sexually dimorphic AVP system. Wild-type (WT) and ArKO male mice were perfused 48 h after an i.c.v. colchicine injection and brain sections were then processed for AVP immunocytochemistry. A prominent decrease (but not a complete suppression) of AVP-ir structures was observed in the BNST and medial amygdala of ArKO mice by comparison with the WT. Similarly, AVP-ir fibres were reduced in the lateral septum of ArKO mice and but not in the medial preoptic area, a region where the AVP system is not sexually dimorphic in rats. No change was detected in the supraoptic and suprachiasmatic nuclei. However, a decrease in AVP-ir cell numbers was however, detected in one subregion of the paraventricular nucleus. These data support the hypothesis that the steroid-sensitive sexually dimorphic AVP system of the mouse forebrain is mainly under the control of aromatized metabolites of testosterone. [less ▲]

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See detailDopamine activates noradrenergic receptors in the preoptic area
Cornil, Charlotte ULg; Balthazart, Jacques ULg; Motte, Patrick ULg et al

in Journal of Neuroscience (2002), 22(21), 9320-9330

Dopamine (DA) facilitates male sexual behavior and modulates aromatase activity in the quail preoptic area (POA). Aromatase neurons in the POA receive dopaminergic inputs, but the anatomical substrate ... [more ▼]

Dopamine (DA) facilitates male sexual behavior and modulates aromatase activity in the quail preoptic area (POA). Aromatase neurons in the POA receive dopaminergic inputs, but the anatomical substrate that mediates the behavioral and endocrine effects of DA is poorly understood. Intracellular recordings showed that 100 muM DA hyperpolarizes most neurons in the medial preoptic nucleus (80%) by a direct effect, but depolarizes a few others (10%). DA-induced hyperpolarizations were not blocked by D1 or D2 antagonists (SCH-23390 and sulpiride). Extracellular recordings confirmed that DA inhibits the firing of most cells (52%) but excites a few others (24%). These effects also were not affected by DA antagonists (SCH-23390 and sulpiride) but were blocked by alpha(2)-(yohimbine) and alpha(1)-(prazosin) noradrenergic receptor antagonists, respectively. Two dopamine-beta-hydroxylase (DBH) inhibitors (cysteine and fusaric acid) did not block the DA-induced effects, indicating that DA is not converted into norepinephrine (NE) to produce its effects. The pK(B) of yohimbine for the receptor involved in the DA- and NE-induced inhibitions was similar, indicating that the two monoamines interact with the same receptor. Together, these results demonstrate that the effects of DA in the POA are mediated mostly by the activation of alpha(2) (inhibition) and alpha(1) (excitation) adrenoreceptors. This may explain why DA affects the expression of male sexual behavior through its action in the POA, which contains high densities of alpha(2)-noradrenergic but limited amounts of DA receptors. This study thus clearly demonstrates the existence of a cross talk within CNS catecholaminergic systems between a neurotransmitter and heterologous receptors. [less ▲]

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