Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor

Thaddeus Wesley Warren Pace, Robert L. Spencer

Research output: Contribution to journalArticle

48 Citations (Scopus)

Abstract

Glucocorticoid negative feedback regulation of the hypothalamic-pituitary- adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng · 10 μl -1 · 2 h-1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.

Original languageEnglish (US)
JournalAmerican Journal of Physiology - Endocrinology and Metabolism
Volume288
Issue number6 51-6
DOIs
StatePublished - Jun 2005
Externally publishedYes

Fingerprint

Mineralocorticoid Receptors
Corticosterone
Psychology
Glucocorticoid Receptors
Feedback
Plasmas
Glucocorticoids
Mineralocorticoid Receptor Antagonists
Propylene Glycol
Steroid Receptors
Sprague Dawley Rats
Rats

Keywords

  • Glucocorticoid negative feedback
  • Hypothalamic-pituitary-adrenal axis regulation
  • RU28318

ASJC Scopus subject areas

  • Physiology
  • Endocrinology
  • Biochemistry

Cite this

@article{8ede3239c60c47a2baa7e45b9b3d566b,
title = "Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor",
abstract = "Glucocorticoid negative feedback regulation of the hypothalamic-pituitary- adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng · 10 μl -1 · 2 h-1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.",
keywords = "Glucocorticoid negative feedback, Hypothalamic-pituitary-adrenal axis regulation, RU28318",
author = "Pace, {Thaddeus Wesley Warren} and Spencer, {Robert L.}",
year = "2005",
month = "6",
doi = "10.1152/ajpendo.00521.2004",
language = "English (US)",
volume = "288",
journal = "American Journal of Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "6 51-6",

}

TY - JOUR

T1 - Disruption of mineralocorticoid receptor function increases corticosterone responding to a mild, but not moderate, psychological stressor

AU - Pace, Thaddeus Wesley Warren

AU - Spencer, Robert L.

PY - 2005/6

Y1 - 2005/6

N2 - Glucocorticoid negative feedback regulation of the hypothalamic-pituitary- adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng · 10 μl -1 · 2 h-1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.

AB - Glucocorticoid negative feedback regulation of the hypothalamic-pituitary- adrenal (HPA) axis is mediated by corticosteroid receptors. It is widely thought that during stress, glucocorticoid receptors (GR) are essential for this negative feedback. In contrast, mineralocorticoid receptors (MR) are associated with HPA axis regulation in basal, nonstress conditions. Notions about the relative roles of MR and GR for HPA axis regulation during stressor challenge may not be complete. Recent work in our laboratory suggests that previous estimates of MR occupancy at resting plasma levels of corticosterone (CORT) may be overestimated. It is possible that a significant number of MR may be available to mediate negative feedback during stressor challenge. We hypothesized that this may be especially the case during mild stressor challenge when the plasma CORT response is weak. In the present studies, adult male Sprague-Dawley rats were first treated systemically or centrally with the selective MR antagonist RU28318 (50 mg/kg sc or 500 ng · 10 μl -1 · 2 h-1 icv) or vehicle (300 μl propylene glycol sc or 10 μl/2 h sterile saline icv) and then challenged with 60-min novel environment or restraint. In vehicle controls, restraint resulted in a greater plasma CORT response than novel environment. Both systemic and central treatment with RU28318 significantly increased CORT responding to novel environment relative to vehicle controls. However, RU28318 treatment did not increase the CORT response to restraint. These data suggest that MR may be necessary for glucocorticoid regulation of HPA axis activity during mild stressors, but not during stressors that result in a more robust CORT response.

KW - Glucocorticoid negative feedback

KW - Hypothalamic-pituitary-adrenal axis regulation

KW - RU28318

UR - http://www.scopus.com/inward/record.url?scp=19444365671&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19444365671&partnerID=8YFLogxK

U2 - 10.1152/ajpendo.00521.2004

DO - 10.1152/ajpendo.00521.2004

M3 - Article

C2 - 15671079

AN - SCOPUS:19444365671

VL - 288

JO - American Journal of Physiology

JF - American Journal of Physiology

SN - 0363-6143

IS - 6 51-6

ER -