Direct Inhibitory effect of glucocorticoids on corticotrophin-releasing hormone gene expression in neurones of the paraventricular nucleus in rat hypothalamic organotypic cultures

B. Bali, S. Ferenczi, Krisztina J. Kovács

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23 Citations (Scopus)

Abstract

Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1μm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin-stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of the rat hypothalamus.

Original languageEnglish
Pages (from-to)1045-1051
Number of pages7
JournalJournal of Neuroendocrinology
Volume20
Issue number9
DOIs
Publication statusPublished - 2008

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Paraventricular Hypothalamic Nucleus
Corticotropin-Releasing Hormone
Glucocorticoids
Gene Expression
Neurons
Messenger RNA
Corticosterone
Dexamethasone
Adrenal Cortex Hormones
Colforsin
Hypothalamus
Third Ventricle
Sodium Channels
Steroid Receptors
Tetrodotoxin
Action Potentials
In Situ Hybridization

Keywords

  • Corticosterone
  • Dexamethasone
  • DRB
  • Forskolin
  • In vitro
  • Tetrodotoxin

ASJC Scopus subject areas

  • Endocrinology
  • Neuroscience(all)

Cite this

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title = "Direct Inhibitory effect of glucocorticoids on corticotrophin-releasing hormone gene expression in neurones of the paraventricular nucleus in rat hypothalamic organotypic cultures",
abstract = "Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1μm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin-stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of the rat hypothalamus.",
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T1 - Direct Inhibitory effect of glucocorticoids on corticotrophin-releasing hormone gene expression in neurones of the paraventricular nucleus in rat hypothalamic organotypic cultures

AU - Bali, B.

AU - Ferenczi, S.

AU - Kovács, Krisztina J.

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N2 - Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1μm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin-stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of the rat hypothalamus.

AB - Corticotrophin-releasing hormone (CRH) in the parvocellular neurosecretory neurones of hypothalamic paraventricular nucleus governs neuroendocrine stress cascade and is the major target of the negative feedback effect of corticosteroids. To assess whether glucocorticoids exert their inhibitory effect on CRH expression directly on parvocellular neurones or indirectly through a complex neuronal circuit, we examined the effect of corticosterone (CORT) and dexamethasone (DEX) on CRH mRNA levels in slice explant cultures of the rat hypothalamus. Organotypic slice cultures were prepared from 6 days old rat pups and maintained in vitro for 14 days. CRH mRNA expression was measured by in situ hybridisation histochemistry. Under basal conditions, CRH mRNA expressing cells were exclusively revealed in the paraventricular region along the third ventricle. Inhibition of action potential spike activity by tetrodotoxin (TTX, 1μm) reduced CRH mRNA signal in the organotypic cultures. CORT (500 nm) or DEX (50 nm) treatment for 24h significantly inhibited CRH expression in the parvocellular neurones and this effect of corticosteroids was not affected following blockade of voltage dependent sodium channels by TTX. Forskolin-stimulated CRH mRNA levels in the paraventricular nucleus were also inhibited by CORT or DEX in the presence and in the absence of TTX. These studies identify paraventricular CRH neurones as direct target of corticosteroid feedback. Type II corticosteroid receptor agonists act directly on paraventricular neurones to inhibit basal and forskolin-induced CRH mRNA expression in explant cultures of the rat hypothalamus.

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