Cited by 8Treatment of Major DepressionStress Responses and CortisolEstrogen and related hormone effects

The antidepressant-like effect of the 3β-hydroxysteroid dehydrogenase inhibitor trilostane involves a regulation of β-type estrogen receptors

Espallergues, Julie, Temsamani, Jamal, Laruelle, Claude, Urani, Alexandre, Maurice, Tangui·2011·Psychopharmacology

Abstract

Rationale Trilostane is a competitive inhibitor of 3β-hydroxysteroid dehydrogenase (3β-HSD), which notably converts pregnenolone into progesterone or dehydroepiandrosterone into androstenedione. Trilostane shows antidepressant-like properties in the forced swimming test (FST). The compound, however, induced only moderate effects on neuroactive steroid levels that could be related to its behavioral efficacy.Methods We compared the behavioral effect of trilostane with the other 3β-HSD inhibitor, cyanoketone, and analyzed the putative involvement of the β-type estrogen receptor (ERβ) in its antidepressant effect.Results Trilostane reduced immobility in the FST significantly at 12.5 and 25 mg/kg subcutaneously (s.c.), whereas cyanoketone (0-100 mg/kg s.c.) was ineffective. The negative ER modulator fulvestrant (ICI 182780) dose-dependently blocked the effect of trilostane (25 mg/kg). Trilostane increased circulating estradiol levels in the 12.5-50 mg/kg dose-range, and this effect was unaffected by stress and not shared by cyanoketone (25 mg/kg). The trilostane (25 mg/kg) treatment increased the ERβ mRNA expression in adrenals (+100%) and centrally, in the hippocampus (+330%). Stress and cyanoketone failed to affect ERβ mRNA levels in periphery or in the brain.Conclusions These data demonstrate that the antidepressant-like potential of trilostane is not due to its 3β-HSD inhibiting activity, since it is not shared by cyanoketone, but rather to its estrogenic activity. The compound, which releases estradiol and up-regulates ERβ receptors, could be used as a therapeutic tool to allow an estrogenic facilitation of antidepressant efficacy.

Integrity signals

Registry

Crossref · 10.1007/s00213-010-2053-y

Cites

38 of 38 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Espallergues, J., Temsamani, J., Laruelle, C., Urani, A., & Maurice, T.
Affiliations
  • Inserm (FR)
  • Sanofi (France) (FR)
Corresponding author
Maurice, Tangui
Venue
Psychopharmacology
Published
2010-10-28
Volume
214
Issue
2
Pages
455-463
ISSN
  • 0033-3158 (ISSN-L)
  • 1432-2072
OpenAlex
W2041087822
Cited by
8
References
38
Citations by year
2019: 1 · 2018: 2 · 2016: 1 · 2015: 1 · 2013: 1
FWCI
0.70
Type
journal article
Language
en
Open access
closed
Locations
  • Psychopharmacology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Institut National de la Santé et de la Recherche Médicale
Topics
  • Health Sciences › Medicine › Pharmacology › Treatment of Major Depression
  • Life Sciences › Neuroscience › Behavioral Neuroscience › Stress Responses and Cortisol
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
trilostane, antidepressant-like effects, cyanoketone, estradiol, forced swim test, fulvestrant, hippocampus, adrenal gland, neurosteroids, estrogenic activity, depression
MeSH terms
Fulvestrant, Adrenal Glands, Analysis of Variance, Animals, Antidepressive Agents, Behavior, Animal, Cyanoketone, Dose-Response Relationship, Drug, Enzyme Inhibitors, Estradiol, Estrogen Antagonists, Hippocampus, Male, Motor Activity, RNA, Messenger, Dihydrotestosterone, Swimming, Time Factors, 3-Hydroxysteroid Dehydrogenases, Up-Regulation, Estrogen Receptor beta, Mice

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review