Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons

K. Kovács, A. Földes, Paul E. Sawchenko

Research output: Contribution to journalArticle

151 Citations (Scopus)

Abstract

To identify molecular targets of corticosteroid negative feedback effects on neurosecretory neurons comprising the central limb of the hypothalamo-pituitary-adrenal (HPA) axis, we monitored ether stress effects on corticotropin-releasing factor (CRF) and arginine vasopressin (AVP) heteronuclear RNA (hnRNA) expression in rats that were intact or adrenalectomized (ADX) and replaced with corticosterone (B) at constant levels ranging from nil to peak stress concentrations. Under basal conditions, relative levels of both primary transcripts varied inversely as a function of plasma B titers. In response to stress, the kinetics of CRF hnRNA responses of intact and ADX rats replaced with low B were similar, peaking at 5 min after stress. By contrast, intact rats showed a delayed AVP hnRNA response (peak at 2 hr), the timing of which was markedly advanced in ADX/low B-replaced animals (peak at 5-30 min). Transcription factors implicated in these responses responded similarly. Manipulation of B status did not affect the early (5-15 min) phosphorylation of transcription factor cAMP-response element-binding protein (CREB) but accelerated maximal Fos induction from 2 hr after stress (intact) to 1 hr (ADX). Assays of binding by proteins in hypothalamic extracts of similarly manipulated rats toward consensus CRE and AP-1 response elements supported a role for the stress-induced plasma B increment in antagonizing AP-1, but not CRE, binding. These findings suggest that glucocorticoid negative feedback at the transcriptional levels is exerted selectively on AVP gene expression through a mechanism that likely involves glucocorticoid receptor interactions with immediate-early gene products.

Original languageEnglish
Pages (from-to)3843-3852
Number of pages10
JournalJournal of Neuroscience
Volume20
Issue number10
Publication statusPublished - May 15 2000

Fingerprint

Vasopressins
Glucocorticoids
Arginine Vasopressin
Neurons
Corticotropin-Releasing Hormone
Transcription Factor AP-1
RNA
Transcription Factors
Cyclic AMP Response Element-Binding Protein
Immediate-Early Genes
Glucocorticoid Receptors
Response Elements
Corticosterone
Ether
Carrier Proteins
Adrenal Cortex Hormones
Extremities
Phosphorylation
Gene Expression

Keywords

  • Arginine vasopressin
  • Corticosterone
  • Corticotropin-releasing factor
  • CREB
  • Fos
  • Glucocorticoids
  • Negative feedback
  • Neurosecretory neurons
  • Paraventricular nucleus

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Glucocorticoid negative feedback selectively targets vasopressin transcription in parvocellular neurosecretory neurons. / Kovács, K.; Földes, A.; Sawchenko, Paul E.

In: Journal of Neuroscience, Vol. 20, No. 10, 15.05.2000, p. 3843-3852.

Research output: Contribution to journalArticle

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