References of "Journal of Neuroendocrinology"
     in
Bookmark and Share    
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 12 (0 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 17 (3 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 13 (0 ULg)
Full Text
Peer Reviewed
See detailSexual differentiation of the neuroendocrine mechanisms regulating mate recognition in mammals
Bakker, Julie ULg

in Journal of Neuroendocrinology (2003), 15(6), 615-621

When in breeding condition, male and female mammals seek out and mate with opposite-sex conspecifics. The neural mechanisms controlling mate recognition and heterosexual partner preference are sexually ... [more ▼]

When in breeding condition, male and female mammals seek out and mate with opposite-sex conspecifics. The neural mechanisms controlling mate recognition and heterosexual partner preference are sexually differentiated by the perinatal actions of sex steroid hormones. Many mammalian species use odours to identify potential mates. Thus, sex differences in partner preference may actually reflect sex differences in how male and female mammals perceive socially relevant odours. Two olfactory systems have evolved in vertebrates that differ considerably in their anatomy and function. It is generally believed that the main olfactory system is used to detect a wide variety of volatile odours derived from food prey among many sources, whereas the accessory olfactory system has evolved to detect and process primarily nonvolatile odours shown to influence reproductive behaviours and neuroendocrine functions. Some recent results obtained in oestradiol-deficient aromatase knockout (ArKO) mice that provide evidence for a developmental role of oestradiol in olfactory investigation of volatile body odours are discussed, suggesting that: (i) oestrogens contribute to the development of the main olfactory system and (ii) mate recognition is mediated by the main as opposed to the accessory olfactory system. Thus, sex differences in mate recognition and sexual partner preference may reflect sex differences in the perception of odours by the main olfactory system. [less ▲]

Detailed reference viewed: 7 (1 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 37 (1 ULg)
Full Text
Peer Reviewed
See detailLocalization of oestrogen receptors in the sensory and motor areas of the spinal cord in Japanese quail (Coturnix japonica)
Evrard, H. C.; Balthazart, Jacques ULg

in Journal of Neuroendocrinology (2002), 14(11), 894-903

In Japanese quail, the presence of aromatase (oestrogen synthase) in the dorsal horn of the spinal cord suggests that spinal sensory processes might be controlled by local actions of oestrogens. This is ... [more ▼]

In Japanese quail, the presence of aromatase (oestrogen synthase) in the dorsal horn of the spinal cord suggests that spinal sensory processes might be controlled by local actions of oestrogens. This is supported by the presence of oestrogen receptors and aromatase in the dorsal horn of the spinal cord in rats, and by the alteration of sensitivity by oestrogens in various mammalian species and also in canaries. We investigated whether oestrogens that are locally produced in the quail spinal cord can bind to specific receptors in the vicinity of their site of synthesis. We demonstrate the presence of numerous oestrogen receptor alpha-immunoreactive (ERalpha-ir) cell nuclei, predominantly in laminae II and, to a lesser extent, I and III of the dorsal horn of the spinal cord (i.e. in the area where aromatase was previously identified). ERalpha-ir cells were also seen in various parts of the intermediate zone (laminae V-VII). This presence of ERalpha-ir cells in the dorsal horn and intermediate zone fits in well with the distribution of ERalpha-ir cells in homologous areas in mammals, including rats. Only a few labelled cells were found in the ventral horn in the cervical, brachial, thoracic and first lumbar segments, but a conspicuous dense group of large ERalpha-ir cells was identified in lamina IX of the ventral horn in synsacral segments 8-10, which contain the motoneurones innervating the muscles of the cloacal gland. The presence of ERalpha-ir cells in lamina IX of these synsacral segments in quail contrasts with the finding that motoneurones innervating penile muscles in rats contain androgen, but not oestrogen receptors, and are influenced by androgens rather than by oestrogens. Together, these data suggest that spinal actions of oestrogens may modulate the sensory and motor systems that participate in reproduction, as well as other nonreproductive functions in quail. [less ▲]

Detailed reference viewed: 17 (0 ULg)
Full Text
Peer Reviewed
See detailSexually dimorphic activation of galanin neurones in the ferret's dorsomedial preoptic area/anterior hypothalamus after mating
Bakker, Julie ULg; Woodley, S. K.; Kelliher, K. R. et al

in Journal of Neuroendocrinology (2002), 14(2), 116-125

Male ferrets in breeding condition possess three times as many galanin-immunoreactive (IR) neurones as oestrous females in the sexually dimorphic dorsomedial preoptic area/anterior hypothalamus (dmPOA/AH ... [more ▼]

Male ferrets in breeding condition possess three times as many galanin-immunoreactive (IR) neurones as oestrous females in the sexually dimorphic dorsomedial preoptic area/anterior hypothalamus (dmPOA/AH). Using Fos-IR as a marker of activation, we investigated whether mating with intromission differentially activates this sexually dimorphic group of galanin-IR neurones in male and female ferrets. Male ferrets that intromitted had a significantly greater percentage of galanin-IR neurones in the dmPOA/AH that were colabelled with nuclear Fos-IR than oestrous females that received an intromission. Intromissive stimulation augmented Fos-IR in an equal percentage of galanin-IR neurones in both sexes in the medial amygdala (MA) and bed nucleus of the stria terminalis (BNST). Peripheral anosmia induced by bilateral occlusion of males' nares did not reduce the mating-induced activation of galanin-IR neurones in the dmPOA/AH, and there was a significant correlation among individual males between intromission duration and the percentage of dmPOA/AH galanin-IR neurones colabelled with Fos-IR. Exposure of castrated, testosterone propionate-treated male ferrets to either soiled bedding or to volatile odours from oestrous females failed to induce nuclear Fos-IR in galanin-IR neurones located in the dmPOA/AH, BNST or MA, suggesting that the mating-induced activation of galanin-IR forebrain neurones in male ferrets depends more on genital-somatosensory than on olfactory inputs. The observed sex dimorphism in the mating-induced activation of galanin-IR neurones in the dmPOA/AH raises the possibility that these neurones perform a mating-dependent function that occurs only in males. [less ▲]

Detailed reference viewed: 10 (2 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 8 (0 ULg)
Full Text
Peer Reviewed
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 ▲]

Detailed reference viewed: 13 (0 ULg)
Full Text
Peer Reviewed
See detailCocaine and Amphetamine-Regulated-Transcript Peptide Mediation of Leptin Stimulatory Effect on the Rat Gonadotropin-Releasing Hormone Pulse Generator in Vitro
Lebrethon, M. C.; Vandersmissen, E.; Gerard, Arlette ULg et al

in Journal of Neuroendocrinology (2000), 12(5), 383-5

Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using explants of the retrochiasmatic hypothalamus from prepubertal male and female rats. Leptin caused a dose-dependent ... [more ▼]

Pulsatile gonadotropin-releasing hormone (GnRH) secretion was studied in vitro using explants of the retrochiasmatic hypothalamus from prepubertal male and female rats. Leptin caused a dose-dependent reduction of the GnRH interpulse interval in both sexes. We studied the effects of cocaine- and amphetamine-regulated transcript (CART) since this peptide was shown recently to mediate the anorectic effects of leptin in the hypothalamus. CART caused a reduction of the GnRH interpulse interval. This effect was prevented using an anti-CART antiserum which could partially overcome leptin stimulatory effects as well. Using hypothalamic explants from Zucker rats homozygous for the leptin receptor mutation ( fa/fa), GnRH pulse frequency was not affected by leptin, while a significant acceleration was caused by the CART-peptide. In conclusion, leptin involves the hypothalamic CART-peptide to stimulate the prepubertal GnRH pulse generator in vitro. [less ▲]

Detailed reference viewed: 6 (1 ULg)
Full Text
Peer Reviewed
See detailCharacterization of the Insulin-Like Growth Factor Axis in the Human Thymus
Kecha, Ouafae; Martens, Henri ULg; Franchimont, Nathalie et al

in Journal of Neuroendocrinology (1999), 11(6), 435-40

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal ... [more ▼]

The components of the insulin-like growth factor (IGF) axis have been investigated in the normal human thymus. Using ribonuclease protection assays (RPA), IGF-II transcripts were detected in the normal human thymus. By reverse transcriptase polymerase chain reaction (RT-PCR) analyses, promoters P3 and P4 were found to be active in the transcription of IGF2 gene within human thymic epithelial cells (TEC). No IGF-II mRNA could be detected in human lymphoid Jurkat T cells with 30 cycles of RT-PCR. By Northern blot analyses, IGFBP-2 to -6 (but not IGFBP-1) were found to be expressed in TEC with a predominance of IGFBP-4. Interestingly, Jurkat T cells only express IGFBP-2 but at high levels. The type 1 IGF receptor was detected in Jurkat T cells but not in human TEC. The identification of the components of the IGF axis within separate compartments of the human thymus adds further evidence for a role of this axis in the control of T-cell development. The precise influence of thymic IGF axis upon T-cell differentiation and immunological self-tolerance however needs to be further investigated. [less ▲]

Detailed reference viewed: 28 (0 ULg)
Full Text
Peer Reviewed
See detailThymic expression of neuroendocrine self-peptide precursors: role in T-cell survival and self-tolerance
Geenen, Vincent ULg; Kecha, Ouafae; Martens, Henri ULg

in Journal of Neuroendocrinology (1998), 10

Detailed reference viewed: 9 (3 ULg)