umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Combined receptor antagonist stimulation of the HPA axis test identifies impaired negative feedback sensitivity to cortisol in obese men
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Medicine.
Show others and affiliations
2009 (English)In: Journal of Clinical Endocrinology and Metabolism, ISSN 0021-972X, E-ISSN 1945-7197, Vol. 94, no 4, 1347-1352 p.Article in journal (Refereed) Published
Abstract [en]

Context: Hypothalamic-pituitary-adrenal (HPA) axis dysregulation may underlie disorders including obesity, depression, cognitive decline and the metabolic syndrome. Conventional tests of HPA axis negative feedback rely on glucocorticoid receptor (GR) agonists such as dexamethasone, but do not test feedback by endogenous cortisol, potentially mediated by both GR and mineralocorticoid receptors (MR).

Objective: To use a combination of GR (RU38486, mifepristone) and MR (spironolactone) antagonists to explore the poorly understood activation of the HPA axis that occurs in obesity.

Design: Double blind, placebo-controlled randomized cross-over study.

Setting: Clinical research facility.

Participants: 15 lean (BMI 22.0+/-1.6 kg/m(2)) and 16 overweight/obese (BMI 30.1+/-3.5 kg/m(2)) men.

Intervention: Subjects attended on four occasions for blood and saliva sampling every 30 minutes between 1800h and 2200h. At 1100h and 1600h before visits subjects took either 200mg spironolactone, 400mg RU38486, 200mg spironolactone + 400mg RU38486, or placebo orally.

Main outcome measures: serum cortisol levels following drug or placebo.

Results: Cortisol levels did not differ between lean and obese following placebo. Spironolactone and RU38486 alone had modest effects, increasing cortisol by <50% in both groups. However, combined spironolactone plus RU38486 elevated cortisol concentrations substantially, moreso in lean than obese men (2.9(0.3) vs 2.2(0.3) fold elevation, p=0.002).

Conclusions: Combined receptor antagonist stimulation of the HPA axis reveals redundancy of MR and GR in negative feedback in humans. Obese men have impaired responses to combined receptor antagonist stimulation, suggesting impaired negative feedback by endogenous cortisol. Such an approach may be useful to dissect abnormal HPA axis control in neuropsychiatric and other disorders.

Place, publisher, year, edition, pages
2009. Vol. 94, no 4, 1347-1352 p.
Identifiers
URN: urn:nbn:se:umu:diva-19018DOI: 10.1210/jc.2008-2054PubMedID: 19141586OAI: oai:DiVA.org:umu-19018DiVA: diva2:201180
Available from: 2009-03-03 Created: 2009-03-03 Last updated: 2017-12-13Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Mattsson, CeciliaSimonyte, KotrynaOlsson, Tommy
By organisation
Medicine
In the same journal
Journal of Clinical Endocrinology and Metabolism

Search outside of DiVA

GoogleGoogle Scholar

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 218 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf