Skip to main content
Log in

Hypothalamic mechanisms mediating glutamate effects on the hypothalamo-pituitary-adrenocortical axis

  • Published:
Journal of Neural Transmission Aims and scope Submit manuscript

Summary

The effect of local administration of glutamate into the hypothalamic paraventricular nucleus (PVN) on the hypothalamo-pituitary adrenocortical (HPA) axis was studied in male rats. Glutamate caused CRH-41 depletion from the median eminence (ME) and a consequent rise in ACTH and corticosterone (CS) serum levels. In rats pretreated with systemic dexamethasone (dex) these effects were completely inhibited. The administration of the glucocorticoid receptor antagonist RU-38486 abolished the inhibitory effect of dex on the adrenocortical discharge. In addition, the depletion of hypothalamic norepinephrine (NE) and serotonin (5-HT) by specific neurotoxins administered into the ventral noradrenergic blundle or into the raphe nuclei respectively, inhibited the response of serum ACTH and CS following PVN glutamate administration. These data indicate that glutamate stimulated the HPA axis via the release of ME CRH-41 into the portal circulation. This response is steroid sensitive involving type II glucocorticoid receptors. Hypothalamic NE and 5-HT participate in the glutamate induced HPA axis activation.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  • Brann DW (1995) Glutamate: a major excitatory transmitter in neuroendocrine regulation. Neuroendocrinology 61: 213–225

    Google Scholar 

  • Chautard T, Boudouresque F, Guillaume V, Oliver C (1993) Effect of excitatory amino acid on the hypothalamo-pituitary-adrenal axis in the rat during the stress-hyporesponsive period. Neuroendocrinology 57: 70–78

    Google Scholar 

  • Cunningham ET, Sawchenko PE (1988) Anatomical specificity of noradrenergic inputs to the paraventricular and supraoptic nuclei of the rat hypothalamus. J Comp Neurol 274: 60–76

    Google Scholar 

  • Darlington DN, Miyamoto M, Keil LC, Dallman MF (1989) Paraventricular stimulation with glutamate elicits bradycardia and pituitary responses. Am J Physiol 256: R112-R119

    Google Scholar 

  • Farah JN, Rao TS, Mick SJ, Coyne KE, Iyengar S (1991) N-methyl-D-aspartate treatment increases circulating adrenocorticotropin and luteinizing hormone in the rat. Endocrinology 128: 1875–1880

    Google Scholar 

  • Feldman S, Weidenfeld J (1993) Hypothalamic norepinephrine depletion inhibits CRH-41 release following neural stimuli. Neuro Report 5: 258–260

    Google Scholar 

  • Feldman S, Weidenfeld J (1993) Medial posterior hypothalamic input is involved in adrenocortical activation following forebrain limbic stimulation. Neuroscience 53: 223–227

    Google Scholar 

  • Feldman S, Weidenfeld J (1995) Neural mechanisms involved in the corticosteroid feedback effects on the hypothalamo-pituitary-adrenocortical axis. Prog Neurobiol 45: 129–141

    Google Scholar 

  • Feldman S, Weidenfeld J (1995) Posterior hypothalamic deafferentation of 5,7-dihydroxytryptamine inhibit corticotropin-releasing hormone, ACTH and corticosteorne responses following photic stimulation. Neurosci Lett 198: 143–145

    Google Scholar 

  • Feldman S, Conforti N, Melamed E (1986) Norepinephrine depletion in the paraventricular nucleus inhibits the adrenocortical responses to neural stimuli. Neurosci Lett 64: 191–195

    Google Scholar 

  • Feldman S, Conforti N, Melamed E (1987) Paraventricular nucleus serotonin mediates neurally stimulated adrenocortical secretion. Brain Res Bull 18: 165–168

    Google Scholar 

  • Feldman S, Conforti N, Melamed E (1988) Hypothalamic norepinephrine mediates limbic effects on adrenocortical secretion. Brain Res Bull 21: 587–690

    Google Scholar 

  • Feldman S, Saphier D, Weidenfeld J (1992) Corticosterone implants in the paraventricular nucleus inhibit ACTH and corticosterone responses and the release of corticotropin-releasing factor following neural stimuli. Brain Res 578: 251–255

    Google Scholar 

  • Feldman S, Conforti N, Weidenfeld J (1995) Limbic pathways and hypothalamic neurotransmitters mediating adrenocortical responses to neural stimuli. Neurosci Biobehav Rev 19: 235–240

    Google Scholar 

  • Felice LJ, Felice JD, Kissinger PT (1978) Determination of catecholamines in rat brain parts of reversed phase ion-pair liquid chromatography. J Neurochem 31: 1461–1466

    Google Scholar 

  • Gabr RW, Birkle DL, Azzaro AJ (1995) Stimulation of the amygdala by glutamate facilitates corticotropin-releasing factor release from the median eminence and activation of the hypothalamic-pituitary-adrenal axis in stressed rats. Neuroendocrinology 62: 333–339

    Google Scholar 

  • Jezova D, Tokarev D, Rusnak M (1995) Endogenous excitatory amino acids are involved in stress-induced adrenocorticotropin and catecholamine release. Neuroendocrinology 62: 326–332

    Google Scholar 

  • Joanny P, Steinberg J, Zamora AJ, Conte-Devlox B, Millet Y, Oliver C (1989) Corticotropin-releasing factor release from in vitro superfused and incubated rat hypothalamus. Effect of potassium, norepinephrine, and dopamine. Peptides 10: 903–911

    Google Scholar 

  • Jones MT, Gillham B, Campbell EA, Al-Taher ARH, Chuang TT, Di Sciull A (1987) Pharmacology of neural pathways affecting CRH secretion. Ann NY Acad Sci 512: 162–175

    Google Scholar 

  • Kiss A, Aguilera G (1992) Participation of α1-adrenergic receptors in the secretion of hypothalamic corticotropin-releasing hormone during stress. Neuroendocrinology 56: 153–160

    Google Scholar 

  • Kovacs K, Kiss JZ, Makara GB (1986) Glucocorticoid implants around the hypothalamic paraventricular nucleus prevent the increase of corticotropin-releasing factor and arginine vasopressin immunostaining induced by adrenalectomy. Neuroendocrinology 44: 229–234

    Google Scholar 

  • Mandelbrod I, Feldman S, Werman R (1974) Inhibition of firing is the primary effect of microelectrophoresis of cortisol to units in the rat tuberal hypothalamus. Brain Res 80: 303–315

    Google Scholar 

  • Orliaguet G, Parsadaniantz MS, Lenoir V, Duval P, Kerdelhue B (1995) Norepinephrine but not epinephrine stimulates the release of corticotropin-releasing factor from in vitro superfused rat hypothalamus. J Neurosci Res 42: 236–241

    Google Scholar 

  • Plotsky PM (1987) Facilitation of immunoreactive corticotropin-releasing factor secretion into the hypophysial-portal circulation after activation of catecholaminergic pathways or central norepinephrine injections. Endocrinology 121: 924–930

    Google Scholar 

  • Plotsky PM, Cunningham ET, Widmaier EP (1989) Catecholaminergic modulation of corticotropin-releasing factor and adrenocorticotropin secretion. Endocrinol Rev 10: 437–458

    Google Scholar 

  • Reinhard JF, Moskovitz MA, Sved AF, Fernstrom JD (1980) A simple sensitive and reliable assay for serotonin and 5-HIAA in brain tissue using liquid chromatography with electrochemical detection. Life Sci 97: 905–911

    Google Scholar 

  • Saphier D, Feldman S (1988) Ionotrophoretic application of glucocorticoids inhibits identified neurones in the rat paraventricular nucleus. Brain Res 453: 183–190

    Google Scholar 

  • Saphier D, Feldman S (1990) Iontophoresis of cortisol inhibits responses of identified paraventricular nucleus neurones to sciatic nerve stimulation. Brain Res 536: 159–162

    Google Scholar 

  • Sawchenko PE (1987) Adrenalectomy-induced enhancement of CRF and vasopressin immunoreactivity in parvocellular neurosecretory neurons: anatomic, peptide and steroid specificity. J Neurosci 7: 1093–1106

    Google Scholar 

  • Smelik PG, Vermes I (1980) The regulation of the pituitary-adrenal system in mammals. In: Jones IC, Henderson IW (eds) General, comparative and clinical endocrinology of the adrenal cortex. Academic Press, London, pp 1–55

    Google Scholar 

  • van den Pol AN, Trombley PQ (1993) Glutamate neurons in hypothalamus regulate excitatory transmission. J Neurosci 13: 2829–2836

    Google Scholar 

  • Weidenfeld J, Rougeot C, Dray F, Feldman S (1989) Adrenocortical response following acute neurogenic stimuli is mediated by CRF-41. Neurosci Lett 107: 189–194

    Google Scholar 

  • Wuarin JP, Dudek FE (1991) Excitatory amino acid antagonists inhibit synaptic responses in the guinea pig hypothalamic paraventricular nucleus. J Neurophysiol 65: 946–951

    Google Scholar 

  • Yang B, Wang Y, Cynader MS (1996) Synergistic interactions between noradrenaline and glutamate in cytosolic calcium influx in cultured visual cortical neurons. Brain Res 72: 181–190

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Feldman, S., Weidenfeld, J. Hypothalamic mechanisms mediating glutamate effects on the hypothalamo-pituitary-adrenocortical axis. J. Neural Transmission 104, 633–642 (1997). https://doi.org/10.1007/BF01291881

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01291881

Keywords

Navigation