The Society for Integrative and Comparative Biology
Rapid Central Corticosteroid Effects: Evidence for Membrane Glucocorticoid Receptors in the Brain1
1 Neurobiology Division of the Department of Cell and Molecular Biology
2 Neuroscience Program, Tulane University, New Orleans, Louisiana 70118-5698
 |
SYNOPSIS |
|---|
TOP
 SYNOPSIS INTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
Glucocorticoid secretion occurs in a circadian pattern and in response to stress. Among the broad array of glucocorticoid actions are multiple effects in the brain, including negative feedback regulation of hypothalamic hormone secretion. The negative feedback of glucocorticoids occurs on both rapid and delayed time scales, reflecting different regulatory mechanisms. While the slow glucocorticoid effects are widely held to involve regulation of gene transcription, the rapid effects are too fast to invoke genomic mechanisms. We provide a brief overview of multiple lines of evidence for membrane-associated glucocorticoid receptors in the brain, with an emphasis on our recent findings of a rapid, G protein-dependent glucocorticoid action in the rat hypothalamus. We have observed a novel mechanism of rapid glucocorticoid inhibition of parvocellular neuroendocrine cells of the hypothalamic paraventricular nucleus (PVN) mediated by the retrograde release of endocannabinoids and suppression of synaptic glutamate release. This acute glucocorticoid action may underlie the rapid inhibitory effect of glucocorticoids on hypothalamic neuroendocrine function, and provides a potential model for the rapid glucocorticoid effects that occur in several areas of the brain.
|
INTRODUCTION |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
In addition to the classical delayed actions of glucocorticoids that rely on transcriptional regulation, it is becoming increasingly clear that glucocorticoids, like other steroid hormones, also have rapid actions both in peripheral tissues and in the central nervous system. Glucocorticoids have been shown to exert fast effects on the brain to regulate various centrally controlled functions in different species, including stress-related locomotor activity (Sandi et al., 1996
), sexual behavior (Rose et al., 1993), learning and memory (de Quervain et al., 1998), and hypothalamic hormone secretion (Jones et al., 1977; Liu et al., 1995; Papanek et al., 1997). A major role of glucocorticoids is to provide negative feedback regulation of hypothalamic hormone systems, seen especially in the control of the stress hormone, corticotropin releasing hormone (CRH) (see Keller-Wood and Dallman, 1984 for review), but also in that of other hypothalamic hormones, such as vasopressin (Papanek and Raff, 1994) and thyrotropin releasing hormone (TRH) (Brabant et al., 1987). We present here a brief overview of the evidence for rapid corticosteroid signaling through activation of putative membrane glucocorticoid receptors in different parts of the brain and in different vertebrate species, with an emphasis on rapid feedback effects in the hypothalamus. This review is not intended to present an exhaustive survey of the literature, but to provide an overview of recent findings supporting the existence of membrane glucocorticoid receptors in the brain and their link to G protein signaling mechanisms. |
THE HYPOTHALAMIC-PITUITARY-ADRENAL AXIS |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
Glucocorticoids are released from the adrenal cortex in response to activation of the hypothalamic-pituitary-adrenal (HPA) axis. Activation of the HPA axis consists of stimulation of parvocellular neuroendocrine cells in the PVN and the release of the hypophysiotropic hormones CRH and vasopressin into the pituitary portal plexus. These hormones then stimulate the release of adrenocorticotropic hormone (ACTH) from the anterior lobe of the pituitary gland, which accesses the adrenal cortex via the general circulation to cause the secretion of glucocorticoids. Glucocorticoid levels in the blood fluctuate in a diurnal pattern, with relatively high levels found in the circadian morning in humans and low levels at night (rodents and other nocturnal animals show the opposite circadian pattern). Activation of the HPA axis occurs in response to both physiological and psychological stresses. Stress activation of the HPA axis is characterized by circulating levels of glucocorticoids that reach micromolar concentrations.
Glucocorticoids secreted by the adrenal glands in response to stress activation of the HPA axis exert widespread actions that serve to coordinate a variety of responses in the organism appropriate to the demands of a stressful situation. While these actions are probably not fast enough to contribute to the immediate sympathetic fight-or-flight response necessary for survival in the face of an immediate threat, they are fast enough to set the tone for sustaining short-term behavioral adaptations necessary for survival in a dangerous situation. The multiple somatic actions of stress-elevated circulating glucocorticoid levels include, among others, reduced glucose storage and enhanced glucose metabolism, suppression of immune system function, and inhibition of the inflammatory response to injury. Glucocorticoids released during stress also exert profound effects on endocrine function by acting both in the periphery and in the brain. Of particular interest for the purpose of this review are the relatively rapid glucocorticoid effects on hypothalamic neuroendocrine function. Indeed, glucocorticoids have inhibitory effects on different hypothalamic neuroendocrine systems, including but not limited to the negative feedback regulation of the HPA axis by suppression of the secretion of CRH and vasopressin from PVN parvocellular neurons (de Kloet, 2000; Herman et al., 1996). The glucocorticoid negative feedback regulation of the HPA axis occurs both rapidly, by inhibiting CRH release, as well as more slowly, via down-regulation of CRH and vasopressin expression in PVN neurons (Keller-Wood and Dallman, 1984). The canonical transcriptional actions of glucocorticoids are mediated by supposed diffusion of the steroid hormone across the cell membrane and its binding to cytosolic corticosteroid receptors. The interaction of the steroid with its receptor forms a receptor-ligand complex and triggers the translocation of the receptor to the nucleus, where it binds to a hormone response element and regulates gene transcription (Falkenstein et al., 2000). These classical transcriptional effects of glucocorticoids are not the subject of this review, but rather we will address the mechanisms responsible for the rapid effects of glucocorticoids, focusing on recent evidence for putative membrane glucocorticoid receptors. Findings from studies in several different animal models suggest that rapid glucocorticoid actions in the brain are mediated by membrane receptors and non-transcriptional signaling mechanisms.
|
RAPID GLUCOCORTICOID ACTIONS IN THE BRAIN |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
Moore and colleagues first presented evidence for high-affinity membrane corticosteroid receptors in the salamander brain over ten years ago (Orchinik et al., 1991
), and these receptors have since been detected in the brains of several other species of amphibians (Moore et al., 1995; Orchinik et al., 2000) and birds (Breuner and Orchinik, 2001). Brain membrane corticosteroid receptors have been studied primarily in medullary neurons that control male reproductive behavior in the newt (Rose et al., 1993), although they have been detected in other areas of the central nervous system as well (Moore and Rose, 2002: Lewis and Rose, 2003). Interestingly, the membrane glucocorticoid receptors in house sparrows undergo seasonal changes in expression that could be responsible for seasonal variability in the stress response (Wingfeld et al., 1992). In the salamander, the putative membrane corticosteroid receptor has been partially purified and characterized as a 63 kDa protein (Evans et al., 2000a). It differs from the intracellular corticosteroid receptors in its pharmacological profile, having the highest sensitivity to corticosterone and cortisol, but relatively low sensitivity to dexamethasone (Orchinik et al., 1991). The receptor also has been shown to exhibit characteristics of a G protein-coupled receptor in that binding to the receptor is attenuated in the presence of non-hydrolyzable guanine nucleotides and positively correlated to Mg2+ concentration (Orchinik et al., 1992). The receptor exhibits partial pharmacological overlap with kappa and orphanin FQ opioid receptors, suggesting either that it is structurally similar to these receptors, at least in its ligand binding site, or that corticosteroids may act at opioid receptors in the amphibian brain (Evans et al., 2000b). It is interesting to note in light of our recent findings in the mammalian hypothalamus (Di et al., 2003) that preliminary findings in the male newt indicate that the corticosterone-mediated inhibition of clasping behavior mediated by activation of a putative membrane glucocorticoid receptor is antagonized by blocking cannabinoid receptors (Coddington and Moore, 2002), implicating a role for endocannabinoids in the signaling of these receptors that may be similar to that in the mammalian hypothalamus, described below. |
RAPID GLUCOCORTICOID ACTIONS IN THE MAMMALIAN BRAIN |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
Corticosteroid binding to membrane fractions and rapid effects of corticosteroids on neuronal membranes have also been reported in mammalian brain preparations, suggesting actions at membrane corticosteroid receptors. Specific binding of glucocorticoids was found in rat synaptosomal membranes (Towle and Sze, 1983
; Guo et al., 1995), and was developmentally regulated, increasing with age through adolescence (Sze and Towle, 1993). In vivo extracellular electrophysiological studies showed rapid effects of corticosterone administered iontophoretically in the rat brain stem reticular formation (Avanzino et al., 1987a) and locus coeruleus (Avanzino et al., 1987b). The corticosterone effect was found to be primarily excitatory in the locus coeruleus, causing increased spiking activity in 73% and no effect in 27% of recorded neurons, and differed as a function of the region of the brain stem reticular formation, generating primarily an excitatory response in neurons in the caudal reticular formation and an inhibitory response in neurons of the rostral reticular formation. Rapid corticosteroid effects have also been seen in neurons of the rostral ventrolateral medulla (RVLM) recorded in vivo (Rong et al., 1999). Here, too, the predominant effect of corticosteroid was found to be excitatory, nearly 60% of baroreceptive neurons and 75% of the spinal cord-projecting neurons recorded in the RVLM responding to iontophoretic application of corticosterone with an increase in firing frequency. The rapid effects of corticosterone in these studies indicated that the steroid was not signaling through the genome, and implicated a membrane corticosteroid receptor. Thus, the predominant rapid effect of corticosteroids in the mammalian brain stem in vivo appears to be excitatory, stimulating putative cardiovascular, serotonergic and reticular activating neurons through activation of putative membrane receptors. These rapid effects of corticosterone in the brain stem suggest that corticosteroids may contribute to the establishment or maintenance of a state of behavioral arousal during stress.
Studies of corticosteroid effects in vitro have demonstrated rapid modulation of voltage-gated Ca2+ currents in neurons mediated by G protein- and protein kinase-dependent mechanisms. Thus whole-cell patch clamp recordings in dissociated hippocampal CA1 neurons revealed a rapid inhibitory effect of corticosterone on L- and N-type Ca2+ currents (ffrench-Mullen, 1995). This effect was suppressed by pertussis toxin and by intracellular blockade of G protein signaling and protein kinase C, suggesting that it was dependent on the activation of a receptor coupled to Gi/o and the protein kinase C signaling pathway. A recent combined patch clamp and Ca2+ imaging study of neurons dissociated from dorsal root ganglia showed a similar rapid inhibition of voltage-gated Ca2+ currents by corticosterone (He et al., 2003). This effect of corticosterone was also blocked by pertussis toxin pretreatment and by inhibitors of protein kinase C activity, suggesting that corticosteroids may have a generalized inhibitory effect on high voltage-activated Ca2+ currents that is dependent on the activation of a receptor coupled to Gi/o and protein kinase C.
|
RAPID GLUCOCORTICOID ACTIONS IN THE MAMMALIAN HYPOTHALAMUS |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
The inhibitory feedback effects of glucocorticoids on hypothalamic hormone secretion are both rapid, occurring and dissipating within minutes, and delayed, taking several minutes to hours and lasting for days. While the delayed glucocorticoid effects are widely held to involve canonical steroid regulation of gene transcription, the rapid effects are too fast to invoke transcriptional regulation and have long been thought to be caused by a non-genomic mechanism. Several in vivo and in vitro electrophysiological studies have been conducted in the hypothalamus, focusing primarily on the parvocellular neuroendocrine cells of the PVN, in an attempt to determine the mechanism of the fast glucocorticoid inhibition of the HPA axis.
Early in vivo extracellular recordings from PVN neurons projecting to the median eminence (i.e., putative parvocellular neuroendocrine cells) showed rapid responses to iontophoretic application of corticosteroids directly into the PVN (Kasai et al., 1988; Saphier and Feldman, 1988; Li et al., 1991). Although there was not complete consensus in these studies with respect to the valence of the corticosteroid response, both excitatory and inhibitory responses being reported, the predominant effect appeared to be an inhibition, consistent with a direct, rapid feedback inhibition of corticosteroids on the hypothalamic neurons involved in HPA activation.
Several in vitro studies have also shown rapid electrophysiological effects of corticosteroids on hypothalamic PVN neurons mediated by actions at putative membrane receptors. Although cortisol had little effect on the spiking activity of most neurons recorded extracellularly in the parvocellular region of the PVN in hypothalamic slices (Kasai and Yamashita, 1988a), it suppressed the excitatory effect of norepinephrine-induced activation of these neurons (Kasai and Yamashita, 1988b). This suggested that the rapid inhibitory effect of corticosteroids might be due to actions on presynaptic noradrenergic inputs to the PVN parvocellular neurons. However, another in vitro brain slice study suggested that glucocorticoids might have rapid effects on postsynaptic glutamate and GABA receptors in hypothalamic as well as celiac ganglion neurons, since responses to iontophoretically applied glutamate and GABA were attenuated and enhanced, respectively, by corticosteroids and this effect was not blocked by blocking synaptic transmission (Wang et al., 1996). Corticosteroids were also found to inhibit vasopressin release from brain slices through a non-genomic mechanism (Liu et al., 1995). These studies together, therefore, suggest that the inhibitory effects of corticosteroids on hypothalamic neuroendocrine function occur directly at the level of the PVN and involve a putative membrane glucocorticoid receptor. Corticosteroids appear to target synaptic activation of hypothalamic neurons since they have relatively little effect on resting membrane potential and basal firing rates, but attenuate the noradrenergic activation of the neurons and the modulation of glutamate and GABA responses (although direct cortisol effects on voltage-gated K+ channels have also been reported recently in PVN neurons in slices [Zaki and Barrett-Jolley, 2002]). It is interesting to note here that there is a strong presynaptic noradrenergic regulation of glutamate and GABA release onto PVN parvocellular (Daftary et al., 2000) and magnocellular neurons (Daftary et al., 1998; Wang et al., 1998; Boudaba et al., 2003), and that corticosteroids may affect the activity of PVN neurons by modulating noradrenergic, glutamatergic and/or GABAergic synaptic inputs to these neurons.
Indeed, we recently reported a rapid effect of glucocorticoids on synaptic glutamate currents recorded in putative PVN parvocellular neuroendocrine cells in hypothalamic slices (Di et al., 2003). In this study, dexamethasone and corticosterone suppressed glutamatergic synaptic currents within 
3 min in a dose-dependent fashion, with half-maximal effects occurring at stress corticosteroid levels (367 nM) (Fig. 1). Several lines of evidence suggested that this glucocorticoid effect on PVN parvocellular neurons was mediated by a membrane-associated receptor and a G protein-dependent mechanism (Fig. 2). The glucocorticoid effect was not blocked by antagonists of the intracellular type I and type II corticosteroid receptors. A dexamethasone-bovine serum albumin conjugate (10 µM) retained the inhibitory effect of dexamethasone on mEPSC frequency, and dexamethasone applied directly into the cytoplasm of parvocellular neurons via the patch pipette was without effect. The effect of dexamethasone on glutamate release was blocked by blocking protein kinase activity and, interestingly, by blocking G protein activity specifically in the postsynaptic parvocellular neurons by intracellular infusion of a G protein blocker via the patch pipette. The latter observation suggested that the corticosteroid effect was, in fact, mediated by activation of a receptor located postsynaptically on the parvocellular neurons and by the subsequent release of a retrograde messenger that acted on presynaptic glutamate terminals to suppress glutamate release.
|
|
Endocannabinoids have been shown recently to serve as retrograde messengers in the regulation of synaptic glutamate and GABA release (Auclair et al., 2000
; Wilson and Nicoll, 2001), so we tested for a cannabinoid dependence of the rapid glucocorticoid suppression of glutamate release. We found that the glucocorticoid effect was completely blocked by antagonists of the CB1 cannabinoid receptor and that it was mimicked by a cannabinoid agonist (Fig. 3). These data suggested, therefore, that the rapid retrograde messenger activated by glucocorticoids was an endocannabinoid.
|
These effects of glucocorticoids on excitatory synaptic inputs mediated by endocannabinoid release in the PVN were found in CRH neurons, suggesting direct feedback inhibition of the HPA axis. However, they were also found in other parvocellular PVN neurons identified by single-cell RT-PCR, including thyrotropin releasing hormone (TRH)-, oxytocin- and vasopressin-expressing neurons (Di et al., 2003
). Thus, glucocorticoid-induced suppression of glutamatergic synaptic inputs occurs in different parvocellular neuroendocrine cells of the PVN, which suggests a more generalized inhibitory feedback role of glucocorticoids in the regulation of neuroendocrine function.
These findings point to a rapid corticosteroid action mediated by the activation of a membrane-associated receptor and a G protein/protein kinase-dependent mechanism (Fig. 4A), and corroborate the increasing body of evidence for non-transcriptional corticosteroid effects mediated by putative membrane glucocorticoid receptors. Interestingly, our findings indicate that the activation of these receptors in the PVN leads to the suppression of glutamatergic synaptic inputs to PVN parvocellular neuroendocrine cells via a novel mechanism involving the retrograde release of an endocannabinoid (Fig. 4B). Indeed, we have preliminary evidence from liquid chromatography-mass spectrometry analyses in brain slices indicating that dexamethasone elicits a significant increase in the levels of the endocannabinoids anandamide and 2-arachidonoylglycerol in the rat PVN and supraoptic nucleus, but not in the cerebellum (Malcher-Lopes et al., 2004), which corroborates our electrophysiological findings and supports our model of glucocorticoid suppression of excitatory synaptic inputs to PVN parvocellular neurons via the retrograde release of endocannabinoids (Fig. 4). Additionally, we have preliminary confocal immunohistochemistry data showing colocalization of CB1 cannabinoid receptors with the vesicular glutamate transporter 2, a marker of glutamate synaptic boutons, in the PVN (Di and Tasker, 2003), which suggests CB1 expression in presynaptic glutamatergic synaptic terminals in the PVN and provides further support for our model. Although, at this point, this model seems the most parsimonious for explaining the observed rapid effects of glucocorticoids on synaptic glutamate inputs to PVN neuroendocrine cells, we cannot yet exclude other alternative models that might also account for these observations, including the possibility of a glial cell intermediate and neuronal-glial interactions to stimulate endocannabinoid release.
|
These findings provide a likely mechanism for the rapid feedback inhibition of the HPA axis by glucocorticoids directly at the level of the hypothalamic CRH neurons. However, this effect was also seen in parvocellular neurons of the PVN that express TRH, oxytocin and vasopressin (Di et al., 2003
), and in magnocellular neurons that express oxytocin and vasopressin (Di et al., 2005), indicating that the rapid glucocorticoid inhibition is not limited to the CRH neurons and the HPA axis, but also acts on other neuroendocrine systems, such as the hypothalamic-pituitary-thyroid and the hypothalamic-neurohypophysial axes. Although unexpected, this finding is not surprising considering the evidence for inhibitory effects of glucocorticoids on various neuroendocrine systems (Brabant et al., 1987; Papanek and Raff, 1994; Tsigos and Chrousos, 2002). It suggests that glucocorticoid-induced retrograde endocannabinoid release may be a more generalized mechanism by which stress levels of glucocorticoids exert a rapid inhibitory influence on neuroendocrine function. The fact that both glucocorticoids and endocannabinoids have well-established central orexigenic actions in the control of energy homeostasis (Kirkham et al., 2002; Zakrzewska et al., 1999), and that CRH, TRH, oxytocin and vasopressin have all been shown to regulate metabolic function and feeding behavior (Rondeel et al., 1992; Burlet et al., 1992; Verbalis et al., 1986), suggest that this mechanism may also play an important role in the neuroendocrine regulation and central coordination of stress and feeding.
Although the putative membrane glucocorticoid receptors have not yet been isolated or identified, there is increasing evidence that such receptors exist and that the rapid downstream effects of activation of these receptors depend on G protein signaling mechanisms. Indeed, compelling evidence for membrane progestin and estrogen receptors coupled to G protein signaling pathways has recently been reported (Zhu et al., 2003; Revankar et al., 2005; Thomas et al., 2005), making it more likely that similar receptors that mediate the rapid, membrane-delimited effects of glucocorticoids will be discovered. It remains to be determined whether corticosteroids are the cognate ligand at separate, as-yet unidentified membrane glucocorticoid receptors, or act allosterically at known or unknown receptors of another transmitter or hormone, as has been shown for the neurosteroids and GABAA receptors (Paul and Purdy, 1992) and for progesterone and oxytocin receptors (Grazzini et al., 1998). It is possible that more than one membrane glucocorticoid receptor, or mode of rapid glucocorticoid action, will be found in the brain and other tissues, as there appears to be multiple pharmacological and biochemical profiles of the rapid glucocorticoid effects, some sensitive and others insensitive to the intracellular glucocorticoid receptor antagonist mifepristone (Qi et al., 2005), and some dependent and others independent of cAMP signaling (see Chen and Qiu, 2001 for review). Interestingly, relatively little is known about the glucocorticoid receptor(s) that mediate(s) the rapid effects of corticosteroids (Evans et al., 2000a; Guo et al., 1995). Hopefully, with the recent sequencing of the mouse genome and the increasing array of molecular tools available, the identification and characterization of membrane glucocorticoid receptors are just around the corner.
|
FOOTNOTES |
|---|
1 From the Symposium Recent Developments in Neurobiology presented at the Annual Meeting of the Society for Integrative and Comparative Biology, 5–9 January 2004, at New Orleans, Louisiana.
2 E-mail: tasker{at}tulane.edu
|
References |
|---|
|
TOP
SYNOPSISINTRODUCTIONTHE HYPOTHALAMIC-PITUITARY...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...RAPID GLUCOCORTICOID ACTIONS IN...References |
|---|
Auclair, N., S. Otani, P. Soubrie, and F. Crepel. 2000. Cannabinoids modulate synaptic strength and plasticity at glutamatergic synapses of rat prefrontal cortex pyramidal neurons. J. Neurophysiol, 83:3287-3293.
Avanzino, G. L., R. Ermirio, P. Ruggeri, and C. E. Cogo. 1987a. Effects of corticosterone on neurons of reticular formation in rats. Am. J. Physiol, 253:R25-R30.[Medline]
Avanzino, G. L., R. Ermirio, C. E. Cogo, P. Ruggeri, and C. Molinari. 1987b. Effects of corticosterone on neurones of the locus coeruleus, in the rat. Neurosci. Lett, 80:85-88.[CrossRef][Web of Science][Medline]
Boudaba, C., S. Di, and J. G. Tasker. 2003. Presynaptic noradrenergic regulation of glutamate inputs to rat hypothalamic magnocellular neurons. J. Neuroendocrinol, 15:803-810.[Web of Science][Medline]
Brabant, G., A. Brabant, U. Ranft, K. Ocran, J. Kohrle, R. D. Hesch, and A. von zur Muhlen. 1987. Circadian and pulsatile thyrotropin secretion in euthyroid man under the influence of thyroid hormone and glucocorticoid administration. J. Clin. Endocrinol. Metab, 65:83-88.
Breuner, C. W., and M. Orchinik. 2001. Seasonal regulation of membrane and intracellular corticosteroid receptors in the house sparrow brain. J. Neuroendocrinol, 13:412-420.[CrossRef][Web of Science][Medline]
Burlet, A. J., M. Jhanwar-Uniyal, M. Chapleur-Chateau, C. R. Burlet, and S. F. Leibowitz. 1992. Effect of food deprivation and refeeding on the concentration of vasopressin and oxytocin in discrete hypothalamic sites. Pharmacol. Biochem. Behav, 43:897-905.[CrossRef][Web of Science][Medline]
Chen, Y.-Z., and J. Qiu. 2001. Possible genomic consequence of nongenomic action of glucocorticoids in neural cells. News Physiol. Sci, 16:292-296.
Coddington, E. J., and F. L. Moore. 2002. Sex, stress, and drugs: Vasotocin and corticosterone effects on amphibian sex behavior converge on the cannabinoid system. Soc. Neurosci. Abstr, 189:17.
Daftary, S. S., C. Boudaba, K. Szabó, and J. G. Tasker. 1998. Noradrenergic excitation of magnocellular neurons in the rat hypothalamic paraventricular nucleus via intranuclear glutamatergic circuits. J. Neurosci, 18:10619-10628.
Daftary, S. S., C. Boudaba, and J. G. Tasker. 2000. Noradrenergic regulation of parvocellular neurons in the rat hypothalamic paraventricular nucleus. Neuroscience, 96:743-751.[CrossRef][Web of Science][Medline]
de Kloet, E. R. 2000. Stress in the brain. Eur. J. Pharmacol, 405:187-198.[CrossRef][Web of Science][Medline]
de Quervain, D. J., B. Roozendaal, and J. L. McGaugh. 1998. Stress and glucocorticoids impair retrieval of long-term spatial memory. Nature, 394:787-790.[CrossRef][Medline]
Di, S., R. Malcher-Lopes, V. L. Marchese, N. G. Bazan, and J. G. Tasker. 2005. Rapid glucocorticoid endocarrabinoid release and opposing regulation of glutamate and GABA inputs to hypothalamic magnocellular neurons. Endocrinology, DIO 10.1210/ en.2005-0610.
Di, S., R. Malcher-Lopes, and J. G. Tasker. 2003. Non-genomic glucocorticoid inhibition via endocannabinoid release in the hypothalamus: a fast feedback mechanism. J. Neurosci, 23:4850-4857.
Di, S., and J. G. Tasker. 2003. Cannabinoid regulation of synaptic inputs to hypothalamic neuroendocrine cells. Soc. Neurosci. Abstr, 612:12.
Evans, S. J., T. F. Murray, and F. L. Moore. 2000a. Partial purification and biochemical characterization of a membrane glucocorticoid receptor from an amphibian brain. J. Steroid. Biochem. Mol. Biol, 72:209-221.[CrossRef][Web of Science][Medline]
Evans, S. J., B. T. Searcy, and F. L. Moore. 2000b. A subset of kappa opioid ligands bind to the membrane glucocorticoid receptor in an amphibian brain. Endocrinology, 141:2294-2300.
Falkenstein, E., H. C. Tillmann, M. Christ, M. Feuring, and M. Wehling. 2000. Multiple actions of steroid hormones—a focus on rapid, nongenomic effects. Pharmacol. Rev, 52:513-556.
ffrench-Mullen, J. M. 1995. Cortisol inhibition of calcium currents in guinea pig hippocampal CA1 neurons via G-protein-coupled activation of protein kinase C. J. Neurosci, 15:903-911.[Abstract]
Grazzini, E., G. Guillon, B. Mouillac, and H. H. Zingg. 1998. Inhibition of oxytocin receptor function by direct binding of progesterone. Nature, 392:509-512.[CrossRef][Medline]
Guo, Z., Y. Z. Chen, R. B. Xu, and H. Fu. 1995. Binding characteristics of glucocorticoid receptor in synaptic plasma membrane from rat brain. Funct. Neurol, 10:183-194.[Web of Science][Medline]
He, L. M., C. G. Zhang, Z. Zhou, and T. Xu. 2003. Rapid inhibitory effects of corticosterone on calcium influx in rat dorsal root ganglion neurons. Neuroscience, 116:325-333.[CrossRef][Web of Science][Medline]
Herman, J. P., C. M. Prewitt, and W. E. Cullinan. 1996. Neuronal circuit regulation of the hypothalamo-pituitary-adrenocortical stress axis. Crit. Rev. Neurobiol, 10:371-394.[Web of Science][Medline]
Jones, M. T., E. W. Hillhouse, and J. L. Burden. 1977. Structure-activity relationships of corticosteroid feedback at the hypothalamic level. J. Endocrinol, 74:415-424.
Kasai, M., H. Kannan, Y. Ueta, T. Osaka, K. Inenaga, and H. Yamashita. 1988. Effects of iontophoretically applied cortisol on tuberoinfundibular neurons in hypothalamic paraventricular nucleus of anesthetized rats. Neurosci. Lett, 87:35-40.[CrossRef][Web of Science][Medline]
Kasai, M., and H. Yamashita. 1988a. Inhibition by cortisol of neurons in the paraventricular nucleus of the hypothalamus in adrenalectomized rats; an in vitro study. Neurosci. Lett, 91:59-64.[CrossRef][Web of Science][Medline]
Kasai, M., and H. Yamashita. 1988b. Cortisol suppresses noradrenaline-induced excitatory responses of neurons in the paraventricular nucleus; an in vitro study. Neurosci. Lett, 91:65-70.[CrossRef][Web of Science][Medline]
Keller-Wood, M. E., and M. F. Dallman. 1984. Corticosteroid inhibition of ACTH secretion. Endocr Rev, 5:1-24.[Medline]
Kirkham, T. C., C. M. Williams, F. Fezza, and M. V. Di. 2002. Endocannabinoid levels in rat limbic forebrain and hypothalamus in relation to fasting, feeding and satiation: stimulation of eating by 2-arachidonoyl glycerol. Br. J. Pharmacol, 136:550-557.[CrossRef][Web of Science][Medline]
Lewis, C. M., and J. D. Rose. 2003. Rapid corticosterone-induced impairment of amplectic clasping occurs in the spinal cord of roughskin newts (taricha granulosa). Horm. Behav, 43:93-98.[CrossRef][Medline]
Li, T. Z., C. A. Wang, and Y. Z. Chen. 1991. The rapid effect of the iontophoretically applied cortisol on unit activity of neurons in three brain areas in rats. Sheng Li Xue Bao, 43:280-285.[Medline]
Liu, X., C. A. Wang, and Y. Z. Chen. 1995. Non-genomic effect of glucocorticoid on the release of arginine vasopressin from hypothalamic slices in rats. Neuroendocrinology, 62:628-633.[Web of Science][Medline]
Malcher-Lopes, R., S. Di, N. S. Marcheselli, N. G. Bazan, and J. G. Tasker. 2004. Regulation of endocannabinoid release in the hypothalamus by convergent glucocorticoid- and activity-dependent mechanisms. Soc. Neurosci. Abstr, 892:15.
Moore, F. L., M. Orchinik, and C. Lowry. 1995. Functional studies of corticosterone receptors in neuronal membranes. Receptor, 5:21-28.[Web of Science][Medline]
Moore, F. L., and J. D. Rose. 2002. Sensorimotor processing model: How vasotocin and corticosterone interact and control reproductive behaviors in an amphibian. Horm. Brain and Behav. 515–544.
Orchinik, M., L. Matthews, and P. J. Gasser. 2000. Distinct specificity for corticosteroid binding sites in amphibian cytosol, neuronal membranes, and plasma. Gen. Comp. Endocrinol, 118:284-301.[CrossRef][Web of Science][Medline]
Orchinik, M., T. F. Murray, P. H. Franklin, and F. L. Moore. 1992. Guanyl nucleotides modulate binding to steroid receptors in neuronal membranes. Proc. Natl. Acad. Sci. U.S.A, 89:3830-3834.
Orchinik, M., T. F. Murray, and F. L. Moore. 1991. A corticosteroid receptor in neuronal membranes. Science, 252:1848-1851.
Papanek, P. E., and H. Raff. 1994. Physiological increases in cortisol inhibit basal vasopressin release in conscious dogs. Am. J. Physiol, 266:R1744-1751.[Medline]
Papanek, P. E., C. D. Sladek, and H. Raff. 1997. Corticosterone inhibition of osmotically stimulated vasopressin from hypothalamic-neurohypophysial explants. Am. J. Physiol, 272:R158-162.[Web of Science][Medline]
Paul, S. M., and R. H. Purdy. 1992. Neuroactive steroids. FASEB J, 6:2311-2322.[Abstract]
Qi, A. Q., J. Qiu, L. Xiao, and Y. Z. Chen. 2005. Rapid activation of JNK and p38 by glucocorticoids in primary cultured hippocampal cells. J. Neurosci. Res, 80:510-517.[CrossRef][Web of Science][Medline]
Revankar, C. M., D. F. Cimino, L. A. Sklar, J. B. Arterburn, and E. R. Prossnitz. 2005. A transmembrane intracellular estrogen receptor mediates rapid cell signaling. Science, 307:1625-1630.
Rondeel, J. M., R. Heide, W. J. de Greef, H. van Toor, G. A. van Haasteren, W. Klootwijk, and T. J. Visser. 1992. Effect of starvation and subsequent refeeding on thyroid function and release of hypothalamic thyrotropin-releasing hormone. Neuroendocrinology, 56:348-353.[Web of Science][Medline]
Rong, W., W. Wang, W. Yuan, and Y. Chen. 1999. Rapid effects of corticosterone on cardiovascular neurons in the rostral ventrolateral medulla of rats. Brain Res, 815:51-59.[CrossRef][Web of Science][Medline]
Rose, J. D., F. L. Moore, and M. Orchinik. 1993. Rapid neurophysiological effects of corticosterone on medullary neurons: Relationship to stress-induced suppression of courtship clasping in an amphibian. Neuroendocrinology, 57:815-824.[Web of Science][Medline]
Sandi, C., C. Venero, and C. Guaza. 1996. Novelty-related rapid locomotor effects of corticosterone in rats. Eur. J. Neurosci, 8:794-800.[CrossRef][Web of Science][Medline]
Saphier, D., and S. Feldman. 1988. Iontophoretic application of glucocorticoids inhibits identified neurones in the rat paraventricular nucleus. Brain Res, 453:183-190.[CrossRef][Web of Science][Medline]
Sze, P. Y., and A. C. Towle. 1993. Developmental profile of glucocorticoid binding to synaptic plasma membrane from rat brain. Int. J. Dev. Neurosci, 11:339-346.[CrossRef][Web of Science][Medline]
Thomas, P., Y. Pang, E. J. Filardo, and J. Dong. 2005. Identity of an estrogen membrane receptor coupled to a G protein in human breast cancer cells. Endocrinology, 146:624-632.[Web of Science][Medline]
Towle, A. C., and P. Y. Sze. 1983. Steroid binding to synaptic plasma membrane: Differential binding of glucocorticoids and gonadal steroids. J. Steroid. Biochem, 18:135-143.[CrossRef][Web of Science][Medline]
Tsigos, C., and G. P. Chrousos. 2002. Hypothalamic-pituitary-adrenal axis, neuroendocrine factors and stress. J. Psychosom. Res, 53:865-871.[CrossRef][Web of Science][Medline]
Verbalis, J. G., M. J. McCann, C. M. McHale, and E. M. Stricker. 1986. Oxytocin secretion in response to cholecystokinin and food: Differentiation of nausea from satiety. Science, 232:1417-1419.
Wang, W., B. R. Xing, and Y. Z. Chen. 1996. Fast modulation of glutamate and GABA receptor-mediate electrophysiological responses by glucocorticoid. Sheng Li Xue Bao, 48:551-556.[Medline]
Wang, Y. F., I. Shibuya, N. Kabashima, V. S. Setiadji, T. Isse, Y. Ueta, and H. Yamashita. 1998. Inhibition of spontaneous postsynaptic currents (IPSC) by noradrenaline in rat supraoptic neurons through presynaptic alpha2-adrenoceptors. Brain. Res, 807:61-69.[CrossRef][Web of Science][Medline]
Wilson, R. I., and R. A. Nicoll. 2001. Endogenous cannabinoids mediate retrograde signalling at hippocampal synapses. Nature, 410:588-592.[CrossRef][Medline]
Wingfeld, J. C., C. M. Vleck, and M. C. Moore. 1992. Seasonal changes of the adrenocortical response to stress in birds of the sonoran desert. J. Exp. Zool, 264:419-428.[CrossRef][Web of Science][Medline]
Zaki, A., and R. Barrett-Jolley. 2002. Rapid neuromodulation by cortisol in the rat paraventricular nucleus: An in vitro study. Brit. J. Pharm, 137:87-97.[CrossRef][Web of Science][Medline]
Zakrzewska, K. E., I. Cusin, A. Stricker-Krongrad, O. Boss, D. Ricquier, B. Jeanrenaud, and F. Rohner-Jeanrenaud. 1999. Induction of obesity and hyperleptinemia by central glucocorticoid infusion in the rat. Diabetes, 48:365-370.[Abstract]
Zhu, Y., C. D. Rice, Y. Pang, M. Pace, and P. Thomas. 2003. Cloning, expression, and characterization of a membrane progestin receptor and evidence it is an intermediary in meiotic maturation of fish oocytes. Proc. Natl. Acad. Sci. U.S.A, 100:2231-2236.
CiteULike 
Connotea 
Del.icio.us What's this?
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||