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Updated: Feb 27, 2026
An In Vivo Estrogen Deficiency Mouse Model for Screening Exogenous Estrogen Treatments of Cardiovascular Dysfunction After Menopause
Published on: August 13, 2019
Novel oestrogen receptor β-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice
Daimei Sasayama1, Nobuhiro Sugiyama2,3, Shigeru Yonekubo4
1Department of Psychiatry, Shinshu University School of Medicine, Matsumoto, Nagano, 390-8621, Japan.
Abstract:
Hormonal changes due to menopause can cause various health problems including weight gain and depressive symptoms. Multiple lines of evidence indicate that oestrogen receptors (ERs) play a major role in postmenopausal obesity and depression. However, little is known regarding the ER subtype-specific effects on obesity and depressive symptoms. To delineate potential effects of ERβ activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor β-selective ligand (C-1) in ovariectomized mice. Uterine weight, depressive behaviour, and weight gain were examined in sham-operated control mice and ovariectomized mice administered placebo, C-1, or 17β-oestradiol (E2). Administration of C-1 or E2 reduced body weight gain and depressive-like behaviour in ovariectomized mice, as assessed by the forced swim test. In addition, administration of E2 to ovariectomized mice increased uterine weight, but administration of C-1 did not result in a significant increase in uterine weight. These results suggest that the selective activation of ERβ in ovariectomized mice may have protective effects against obesity and depressive-like behaviour without causing an increase in uterine weight. The present findings raise the possibility of the application of ERβ-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.
Insights
Selective estrogen receptor beta (ERβ) activation may combat postmenopausal weight gain and depression. A novel ERβ-selective ligand (C-1) reduced obesity and depressive behaviors in mice without increasing uterine weight, suggesting a potential new therapeutic approach.
Area of Science:
- Endocrinology
- Neuroscience
- Pharmacology
Background:
- Menopause-induced hormonal shifts contribute to obesity and depression.
- Estrogen receptors (ERs) are implicated in postmenopausal obesity and mood disorders.
- ER subtype-specific roles in these conditions remain largely uncharacterized.
Purpose of the Study:
- To investigate the effects of a novel ERβ-selective ligand (C-1) on obesity and depressive symptoms in a mouse model of menopause.
- To determine if ERβ activation offers therapeutic benefits without adverse effects on uterine weight.
Main Methods:
- Ovariectomized mice were treated with placebo, C-1 (ERβ-selective ligand), or 17β-estradiol (E2).
- Evaluated outcomes included body weight gain, depressive-like behavior (forced swim test), and uterine weight.
Main Results:
- Both C-1 and E2 administration significantly reduced body weight gain and depressive-like behavior in ovariectomized mice.
- E2 treatment increased uterine weight, whereas C-1 treatment did not cause a significant increase.
- Selective ERβ activation demonstrated potential protective effects against obesity and depression without uterine side effects.
Conclusions:
- Selective activation of ERβ may offer a promising therapeutic strategy for managing obesity and depression in postmenopausal women.
- ERβ-selective ligands like C-1 could provide benefits without the uterine-related risks associated with traditional estrogen therapy.
