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G F Ball

Publications and source records attributed to G F Ball.

At least 19 recordsLinked to original sources

Plasticity in the expression of the steroid receptor coactivator 1 in the Japanese quail brain: effect of sex, testosterone, stress and time of the day.

Analysis of nuclear receptor action on the eukaryotic genome highlights the importance of coactivators on gene transcription. The steroid receptor coactivator-1 in particular is the focus of an intense research and physiological or behavioral studies have confirmed that it plays a major role in the modulation of steroid and thyroid receptors activity. However, little is known about the regulation of steroid receptor coactivator-1 expression the brain. The goal of this study was to determine the potential factors modulating steroid receptor coactivator-1 synthesis in Japanese quail by quantification of its mRNA with real time quantitative polymerase chain reaction and of the corresponding protein via Western blotting. Contrary to previously published results from our laboratory [Charlier TD, Lakaye B, Ball GF, Balthazart J (2002) The steroid receptor coactivator SRC-1 exhibits high expression in steroid-sensitive brain areas regulating reproductive behaviors in the quail brain. Neuroendocrinology 76:297-315], we found here that sexually mature females had a higher concentration of steroid receptor coactivator-1 in the preoptic area/hypothalamus compared with males. Steroid receptor coactivator-1 expression in the male preoptic area/hypothalamus was up-regulated by testosterone and tended to be decreased by stress. We also identified a significant correlation between the time of the day and the expression of the coactivator in the optic lobes, hippocampus, telencephalon and hindbrain but the pattern of changes in expression as a function of the time of the day varied from one brain area to another. Together, these data support the idea that steroid receptor coactivator-1 is not constitutively expressed but rather is finely regulated by steroids, stress and possibly other unidentified factors.

Animals↗

Neuroanatomical specificity in the expression of the immediate early gene c-fos following expression of appetitive and consummatory male sexual behaviour in Japanese quail.

We investigated the neural sites related to the occurrence of appetitive (ASB) and consummatory (CSB) aspects of male sexual behaviour in Japanese quail. Castrated males treated with testosterone were exposed for 5 min to one of four experimental conditions: (i) free interaction with a female (CSB group); (ii) expression of rhythmic cloacal sphincter movements in response to the visual presentation of a female (ASB-F group); (iii) or a male (ASB-M group), and (iv) handling as a control manipulation. Brains were collected 90 min after the start of behavioural tests and stained by immunocytochemistry for the FOS protein. An increase in FOS expression was observed throughout the rostro-caudal extent of the medial preoptic nucleus (POM) in CSB males, whereas the view of a female (ASB-F) induced an increased FOS expression in the rostral POM only. In the CSB group, there was also an increase in FOS expression in the bed nucleus striae terminalis, and both the CSB and ASB-F groups exhibited increased FOS expression in aspects of the ventro-lateral thalamus (VLT) related to visual processing. Moreover, both the CSB and ASB-M groups showed increased FOS expression in the lateral septum. These data provide additional support to the idea that there is a partial anatomical dissociation between structures involved in the control of both aspects of male sexual behaviour and independently provide data consistent with a previous lesion study that indicated that the rostral and caudal POM differentially control the expression of ASB and CSB in quail.

Animals↗

Rapid changes in production and behavioral action of estrogens.

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.

Animals↗

Rapid decreases in preoptic aromatase activity and brain monoamine concentrations after engaging in male sexual behavior.

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.

3,4-Dihydroxyphenylacetic Acid↗

Sexual behavior activates the expression of the immediate early genes c-fos and Zenk (egr-1) in catecholaminergic neurons of male Japanese quail.

We analyzed the expression of the immediate early genes c-fos and Zenk (egr-1) in the brain of male quail that were gonadally intact (I) or castrated and treated (CX+T) or not (CX) with testosterone and had been exposed for 60 min either to a sexually mature female (F), or to an empty arena (EA) or were left in their home cage (HC). Alternate sections in the brains collected 90 min after the start of behavioral interactions were stained by immunocytochemistry for the proteins FOS or ZENK alone or in association with tyrosine hydroxylase (TH), a marker of catecholaminergic neurons. C-fos and Zenk expression was statistically increased in six brain areas of sexually active birds (I+F, CX+T+F) compared with controls (CX+F, CX+T+EA, CX+T+HC), i.e. the preoptic area, bed nucleus striae terminalis, arcopallium, nucleus intercollicularis, periaqueductal gray and the ventral tegmental area. Interestingly, c-fos and Zenk expression was high in the nucleus intercollicularis, a midbrain vocal control nucleus, of I+F and CX+T+F birds that displayed copulatory behavior but emitted few crows but not in the nucleus intercollicularis of CX+T+EA birds that crowed frequently. Increases in c-fos expression were observed in TH-immunoreactive cells in the periaqueductal gray and ventral tegmental area, but not in the substantia nigra, of I+F and CX+T+F birds indicating the activation of dopaminergic neurons during sexual behavior. Together, these data confirm the implication of the steroid-sensitive preoptic area and bed nucleus striae terminalis in the control of copulation and support the notion that dopamine is involved in its control.

Animals↗

Interactions between kinases and phosphatases in the rapid control of brain aromatase.

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.

Acid Phosphatase↗

Effects of calmodulin on aromatase activity in the preoptic area.

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.

Amino Acid Sequence↗

Immediate early gene response to hearing song correlates with receptive behavior and depends on dialect in a female songbird.

Stimulus-induced expression of the immediate early gene ZENK (egr-1) in the songbird's auditory forebrain presumably depends on the behavioral significance of the stimulus. Few studies, however, have quantified both the ZENK and behavioral responses to a stimulus in the same individuals. We played conspecific male song of either hatch (local) or foreign dialect to female white-crowned sparrows (Zonotrichia leucophrys oriantha) and quantified both the auditory ZENK response and their behavioral response, which is known to depend on dialect. Birds hearing hatch dialect showed greater ZENK induction in the caudomedial hyperstriatum ventrale and the dorsal portion of the caudomedial neostriatum than birds hearing foreign dialect, supporting previous work showing a relationship between ZENK and salience of the stimulus. In the dorsal portion of the caudomedial neostriatum, ZENK induction was correlated with the amount of non-vocal courtship behavior; however, in the caudomedial hyperstriatum ventrale, ZENK induction was more highly correlated with the females' own vocal behavior and thus may have been partly self-induced. Some females sang and showed a male-like pattern of ZENK induction in their song systems. This study provides the first evidence that the ZENK response in a sensory area to a social stimulus is proportional to the animal's preference for the stimulus.

Animals↗

Song activation by testosterone is associated with an increased catecholaminergic innervation of the song control system in female canaries.

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.

Animals↗

The neuroendocrinology of reproductive behavior in Japanese quail.

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 review here 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 slow genomic and rapid, presumably non-genomic, changes in brain aromatase activity are also briefly discussed.

Animals↗

Photoperiodic and temporal influences on chemosensory induction of brain fos expression in female prairie voles.

Prairie voles (Microtus ochrogaster) typically stop breeding during winter. Male prairie voles respond to winter day lengths with gonadal regression, whereas female voles are relatively unresponsive to photoperiod. Unlike commonly studied laboratory rodents, female prairie voles do not exhibit spontaneous oestrous cycles. Instead, females are induced into oestrus by chemosensory cues from conspecific male urine. The present study investigated the interaction among day length, chemosensory cues and the initial brain responses during oestrus induction in female voles. A single drop of male conspecific urine, saline or skimmed milk was applied to the nares of female prairie voles housed for 9 weeks in either long (LD 16 : 8 h) or short (LD 8 : 16 h) days. Animals were killed 0.5, 1, 2 or 24 h after chemosensory treatment and their brains were processed for Fos immunocytochemistry. Body mass and ovarian fat pad mass were higher, but uterine and ovarian mass were lower, in short-day compared to long-day females. Regardless of photoperiod, Fos- immunoreactivity increased in the granule layer of the accessory olfactory bulb (AOB), the supraoptic nucleus and bed nucleus of the stria terminalis (BNST) (anterior medial) in females treated with male urine compared to the two control groups. Fos staining intensified in the AOB, medial and posterocortical medial amygdala and BNST (posterior ventral), 1 h and 2 h after urine treatment. In the medial preoptic area, anterior and lateral hypothalamus, and ventromedial nucleus of the hypothalamus, Fos-immunoreactivity was elevated in females 2 h after receiving urine. Overall, long-day females displayed higher Fos expression in response to urine than females maintained in short days. These results identify a putative neural circuitry of oestrus induction in this species, and provide an approximate time line of activation in the brain circuit responsible for oestrus induction in prairie voles.

Amygdala↗

Calcium-dependent phosphorylation processes control brain aromatase in quail.

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.

Adenosine Triphosphate↗

Expression of cAMP response element binding protein-binding protein in the song control system and hypothalamus of adult European starlings (Sturnus vulgaris).

In songbirds, the initiation of song behaviour and the neural substrate of this system are highly influenced by gonadal steroids. Receptors for gonadal steroid hormones, such as androgens and oestrogens, have been localized within select nuclei of the song system. An important step in steroid receptor action is the recruitment of nuclear receptor coactivators. The coactivator, cAMP response element binding protein (CREB)-binding protein (CBP), has been implicated in both androgen and oestrogen receptor transactivation. Although the role of CBP in transcriptional mechanisms has been widely studied, little is known about CBP expression in the brain. The association between the distribution of CBP and oestrogen receptors in the hippocampus has been related to long-term memory. However, the distribution of brain CBP has not been related to the expression of gonadal steroid receptors in a system as relevant to reproductive behaviour as the avian song system. Western immunoblotting of European starling (Sturnus vulgaris) brain tissue reveals a band at 265 kDa. Immunohistochemical localization of CBP in starling brain indicates wide, but heterogeneous expression. CBP-immunoreactive (CBP-ir) cells define the boundaries of song control nuclei. In HVc (sometimes called the High Vocal Center) and the robust nucleus of the archistriatum (RA), there is a higher density of CBP-ir cells within the boundaries of these nuclei than in adjacent neostriatum or archistriatum, for HVc and RA, respectively. We also report that the distribution of CBP-ir cells varies among different nuclei within the song control system. CBP-ir cells within area X (also a part of the song system) and HVc are densely packed into clusters, whereas cells can be easily discriminated in RA. CBP is also highly expressed in hypothalamic areas, indicating that areas rich in steroid receptors also contain CBP. These data suggest that CBP is important for modulating transcriptional activities in the song system and other sites in the songbird brain that express gonadal steroid receptors.

Age Factors↗

Gonadal steroid receptor mRNA in catecholaminergic nuclei of the canary brainstem.

Steroid actions in the song system may be modulated by ascending inputs from catecholaminergic (CA) brain nuclei; however, whether these nuclei contain steroid receptors is unknown. Here, we compared the distribution of androgen receptor (AR) and estrogen receptor-alpha (ER-alpha) mRNA with that of tyrosine hydroxylase immunoreactivity (TH-IR) in the brainstems of male canaries. Areas containing AR and ER-alpha mRNA overlapped with areas containing TH-IR cell bodies in the locus ceruleus and the area ventralis of Tsai. The substantia nigra and the midbrain central gray contained both TH-IR and AR mRNA. The presence of AR and ER-alpha within CA cell groups suggests that sex steroid hormones may modulate song production at the site of CA synthesis.

Androgens↗

Sex differences in songbirds 25 years later: what have we learned and where do we go?

About 25 years ago, Nottebohm and Arnold reported that there are profound male-biased sex differences in volume in selected nuclei in telencephalic portions of the song control system. This review focuses on issues related to the cellular bases of these sex differences in volume and comparative studies that might elucidate the function of this variation between the sexes. Studies utilizing a variety of neurohistological methods in several different species to define the boundaries of two key telencephalic song nuclei HVc and the robust nucleus of the archistriatum (RA) all tend to find a sex difference in volume in agreement with Nissl-defined boundaries. Sex differences in volume in nuclei such as HVc and RA are associated with differences in cell size and cell number. Other attributes of the phenotype of cells in these nuclei are also different in males and females such as the number of cells expressing androgen receptors. Comparative studies have been employed to understand the function of these sex differences in the brain. In some songbird species, females sing rarely or not at all, and the brain nuclei that control song are many times larger volume in males than females. In other species, males and females sing approximately equally, and the brain nuclei that control song are approximately equal between the sexes. Recently, statistical methods have been employed to control for phylogenetic effects while comparing the co-evolution of traits. This analysis indicates that the evolution of sex differences in song has co-evolved with the evolution of sex differences in singing behavior in songbird species. Future studies should focus on the function of the smaller song control nuclei of females and investigate the role these nuclei might play in perception as well as in production.

Animals↗

Response biases in auditory forebrain regions of female songbirds following exposure to sexually relevant variation in male song.

In many species of songbirds, individual variation between the songs of competing males is correlated with female behavioral preferences. The neural mechanisms of song based female preference in songbirds are not known. Working with female European starlings (Sturnus vulgaris), we used immunocytochemistry for ZENK protein to localize forebrain regions that respond to sexually relevant variation in conspecific male song. The number of ZENK-ir cells in ventral caudo-medial neostriatum [NCMv] was significantly higher in females exposed to longer songs than in those exposed to shorter songs, whereas variation in the total duration of song exposure yielded no significant differences in ZENK expression. ZENK expression in caudo-medial ventral hyperstriatum [cmHV] was uniformly high in all subjects, and did not vary significantly among the three groups. These results suggest that subregions of NCM in female starlings are tuned to variation in male song length, or to song features correlated therewith. Female starlings exhibit robust behavioral preferences for longer over shorter male songs (Gentner and Hulse; Anim Behav 59:443-458, 2000). Therefore, the results of this study strongly implicate NCM in at least a portion of the perceptual processes underlying the complex natural behavior of female choice.

Acoustic Stimulation↗

The distribution of tyrosine hydroxylase in the canary brain: demonstration of a specific and sexually dimorphic catecholaminergic innervation of the telencephalic song control nulcei.

Singing and the processing of auditory information related to song can be affected by experimental manipulations of catecholamine activity in the brain of zebra finches. We investigated, by immunocytochemistry in the brain of male and female canaries, the distribution of tyrosine hydroxylase (TH), the rate-limiting step in the synthesis of catecholamines. Fibers immunoreactive for TH (TH-ir) were particularly abundant in the lobus parolfactorius, the paleostriatum primitivum, and the nucleus septalis lateralis. A high density of TH-ir basket-like structures was observed in the caudomedial neostriatum, an area involved in song perception and recognition. In most males, a high density of TH-ir fibers outlined the telencephalic song control nuclei including the high vocal center, the nucleus robustus archistriatalis, the nucleus interfascialis, the lateral and medial parts of the magnocellular nucleus of the anterior neostriatum, and area X of the lobus parolfactorius. The higher density of fibers immunoreactive for TH in these nuclei, compared with the surrounding telencephalon, supports the notion that the morphological evolution of the song control nuclei was accompanied by a neurochemical specialization. This specific innervation of the song control regions was, in general, not found in females. The specific presence of high densities of TH-ir fibers in the song system of male canaries and the sex difference of this innervation provide anatomical evidence in support of the claim that dopamine and/or norepinephrine play important roles in the modulation of song learning and production.

Animals↗

The control of preoptic aromatase activity by afferent inputs in Japanese quail.

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.

Afferent Pathways↗