Journal Article Novel oestrogen receptor beta-selective ligand reduces obesity and depressive-like behaviour in ovariectomized mice

Sasayama, Daimei  ,  Sugiyama, Nobuhiro  ,  Yonekubo, Shigeru  ,  Pawlak, Akiko  ,  Murasawa, Hiroyasu  ,  Nakamura, Mie  ,  Hayashi, Morimichi  ,  Ogawa, Takashi  ,  Moro, Makoto  ,  Washizuka, Shinsuke  ,  Amano, Naoji  ,  Hongo, Kazuhiro  ,  Ohnota, Hideki

7p.4663 , 2017-07-05 , NATURE PUBLISHING GROUP
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 ER beta activation in postmenopausal women, we investigated the effects of a novel oestrogen receptor beta-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 17 beta-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 ERa 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 ER beta-ligands such as C-1 as a novel treatment for obesity and depression in postmenopausal women.

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