Central Glucocorticoid Receptor Immunoreactive Neurons: New Insights into the Endocrine Regulation of the Brain (original) (raw)
Related papers
Neuroscience Research, 1996
The localization of glucocorticoid receptor (GR) immunoreactivity and mRNA in the adult rat brain was examined by light microscopic and electron microscopic immunohistochemistries, and in situ hybridization. For the purpose of detailed investigation of the distribution and comparison of GR immunoreactivities and mRNAs, specific polyclonal antibodies against a part of the transcription modulation (TR) domain of rat GR were used in the immunohistochemistry, whereas fluorescein-labeled RNA probes, complementary to the TR domain in the GR cDNA were used in the in situ hybridization. In the rat brain, GR immunoreactivity was predominantly localized in the cell nucleus, and the expression of GR mRNA was detected in the cytoplasm. GR-immunoreactive and GR mRNA-containing cells were widely distributed from the olfactory bulb of the forebrain to the gracile-cuneate nuclei of the medulla oblongata. The highest densities of GR-immunoreactive and mRNA-containing cells were observed in the subfields of cerebral cortex, olfactory cortex, hippocampal formation, amygdala, septal region, dorsal thalamus, hypothalamus, trapezoid body, cerebellar cortex, locus coeruleus and dorsal nucleus raphe. The distributional pattern of GR immunoreactivity in many regions was well-correlated with that of GR mRNA, but in the CA3 and CA4 pyramidal layers of the hippocampus, different localization was noted. The present study provides the groundwork for elucidating the role of GRs in brain function.
Rapid Central Corticosteroid Effects: Evidence for Membrane Glucocorticoid Receptors in the Brain
Integrative and Comparative Biology, 2005
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.
Rapid Central Corticosteroid Effects: Evidence for Membrane Glucocorticoid Receptors in the Brain1
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.
The Journal of Steroid Biochemistry and Molecular Biology, 1994
The cellular distribution of the glucocorticoid receptor (GR) has not yet been firmly established. The extensive literature indicates that GR is present both in the cytoplasm and the cell nucleus, however, some studies have failed to detect cytoplasmic GR. It is still controversial as to whether GR is randomly diffusing in the cytoplasm and nucleus, or if the GR-distribution is organized or controlled in some way, which may be of importance for the transduction of glucocorticoid effects to cells. There is evidence that both non-activated and activated GR is associated with the plasma membrane, a number of cytoplasmic organelles and the nucleus. Both morphological and biochemical evidence show that GR is associated with microtubules during different stages of the cell cycle, i.e. GR co-localizes, co-purifies and co-polymerizes with tubulin. This indicates that GR is structurally linked to the intracellular MT-network which may be of importance in the mechanism of action of glucocorticoid hormones. The literature in this field is reviewed including the reported data on subcellular GR-loca][ization.
Journal of Neuroendocrinology, 1989
n vitro assays using crude synaptosomal membrane preparations from the cortex and cytosolic fraction of hippocampus have shown that in the brain, steroids can bind to the intracellular corticosteroid receptors as well as to the membrane-bound GABAreceptor complex. Corticosteroid, deoxycorticosterone and spironolactone bound with higher affinity to the mineralocorticoid (relative binding affinity (lC,o in nM) 1.2, 3.9 and 4.9, respectively) than to the glucocorticoid receptors (IC50 5.2, 14.0 and 88.0 nM, respectively) in hippocampal cytosol. They enhanced significantly the binding of [35S]t-butylbicyclophosphorothionate to cortical membrane. Steroids such as 3a,5a-tetrahydroxydeoxycorticosterone and 3a-hydroxy-5a-di hydroprogesterone displaced the binding of [35S]t-butylbicyclophosphorothionate with IC5, (in nM) of 236.7 and 315.0, respectively. In the presence of 10 to 12.5 p M added GABA, they bound with higher affinity (lC,o 18.0 and 20.5 nM, respectively). Pentobarbital also bound to this site with I C, , of 430,000 and 240,00OnM, respectively, in the absence and presence of GABA. These compounds also enhanced the binding of [3H]flunitrazepam which was not affected by the presence of added GABA. They showed no affinity for mineralocorticoid or gl ucocorticoid receptors.
The Journal of Steroid Biochemistry and Molecular Biology, 1991
By means of double immunolabeling procedures it has been possible to demonstrate glucocorticoid receptor (GR) immunoreactivity (IR) in large numbers of various peptidergic neurons of the brain including neurons containing gastrointestinal peptides, opioid peptides, and peptides with a hypothalamic hormone function. For each peptide system, however, marked heterogeneities exist among brain regions. Thus, in the neocortex and the hippocampal formation most of the brain peptide neurons lack GR IR, while the same types of peptide neurons in the arcuate and paraventricular nucleus [e.g. neuropeptide Y (NPY), somatostatin (SRIF) and the cholecystokinin (CCK) neurons] possess strong GR IR. Furthermore, in the arcuate, parvocellular part of the paraventricular nuclei and the central amygdaloid nucleus practically all the peptidergic neurons are strongly GR IR, while in the lateral hypothalamus, mainly the neurotensin (NT) and galanin (GAL) IR neurons are GR IR. These marked differences among areas probably reflect functional differences dependent upon their participation in stress regulated circuits. All the paraventricular NT, corticotropinreleasing factor (CRF), growth hormone-releasing factor (GRF), thyrotropin-releasing hormone (TRH) and SRIF IR neurons appear to contain GR IR, while the luteinizing hormone-releasing hormone (LHRH) IR neurons lack GR IR, underlying the importance of glucocorticoids (GC) in controlling endocrine function. Finally, the GC may influence pain and mood control mainly via effects on enkephalin (ENK) neurons especially in the basal ganglia (mood) and on all fl-endorphin (8-END) neurons of the arcuate nucleus, while most of the dynorphin neurons are not directly controlled by GC.
Experimental Brain Research, 1989
The paraventricular nucleus (PVN) of male albino rats was analyzed for the presence of glucocorticoid receptor-like immunoreactivity (GR-LI) in neuropeptide containing neurons. Using immunohistochemistry, coronal sections trough the entire PVN were double-stained with a mouse monoclonal antibody against G R and one of the following antisera: rabbit antiserum to corticotropin releasing factor (CRF), neurotensin (NT), enkephalin (ENK), cholecystokinin (CCK), thyrotropin releasing hormone (TRH), galanin (GAL), peptide histidine isoleucine (PHI), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) or tyrosine hydroxylase (TH). For comparison the occurrence of GR-LI in NT-, SOM-, NPY-or THpositive neurons of the arcuate nucleus was also studied. Our results indicate that GR-LI is present in the parvocellular part of the PVN but not in its magnocellular portion. Virtually every parvocellular neuron in the PVN containing one of the above mentioned peptides was also positive for GR, with the exception of SOM neurons, of which only about two thirds showed detectable levels of GR-LI. All TH-positive, presumably dopamine neurons in the PVN were GR-positive. In the arcuate nucleus all TH-and NPY-positive neurons as well as a large proportion of the SOM-and NT-immunoreactive neurons contained GR-LI.