The estrogenic component of tibolone reduces adiposity in female aromatase knockout mice.
OBJECTIVE
To explore the effects of tibolone on adiposity in the absence of aromatase and determine which of the hormonal properties of tibolone are exerting these effects.


METHODS
In this study, vehicle; tibolone; estrogenic (ethinyl estradiol [EE]), progestogenic (ORG2058), or androgenic (dihydrotestosterone) compounds; or a combination of ORG2058 + EE was administered to 6-month-old ovariectomized aromatase knockout (ArKO) mice for a period of 6 weeks.


RESULTS
In response to tibolone or EE-alone treatments, omental adipose tissue and infrarenal adipose tissue weights were significantly reduced (P = 0.004 and P = 0.01; P = 0.009 and P = 0.014, respectively) compared with those in ovariectomized and vehicle-treated ArKO mice. In contrast, adipose tissue weight tended to increase after ORG2058-alone treatment. Furthermore, EE in the presence of ORG2058 (ORG2058 + EE group) results in little effect on adiposity when compared with that in ovariectomized and vehicle-treated ArKO mice, showing that ORG2058 can negate the effect of EE. Dihydrotestosterone treatment did not have an impact on adipose tissue mass. Adipocyte volume and numbers followed the same treatment trends.


CONCLUSIONS
In summary, our study in the ArKO mouse has confirmed the efficacy of tibolone as a hormone therapy to reduce adipose tissue accumulation after menopause and also shows that aromatization of tibolone is not required to elicit these estrogenic effects.
Van Sinderen
Michelle L
ML
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia.
Boon
Wah Chin
WC
Ederveen
Antwan G H
AG
Kloosterboer
Helenius J
HJ
Simpson
Evan R
ER
Jones
Margaret E E
ME
D050154:Adiposity / Q000187:drug effects* / Q000502:physiology; D045930:Anabolic Agents / Q000494:pharmacology*; D000818:Animals; D001141:Aromatase / Q000378:metabolism*; D005260:Female; D051379:Mice; D018345:Mice, Knockout; D009652:Norpregnenes / Q000494:pharmacology*; D010052:Ovariectomy
D045930:Anabolic Agents; D009652:Norpregnenes; D001141:Aromatase; C027385:tibolone