The estrogenic component of tibolone reduces adiposity in female aromatase knockout mice

  title={The estrogenic component of tibolone reduces adiposity in female aromatase knockout mice},
  author={Michelle L. Van Sinderen and Wah Chin Boon and Antwan G.H. Ederveen and Helenius Jan Kloosterboer and Evan R. Simpson and Margaret E. E. Jones},
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… Expand
Effects of Estrogens on Adipokines and Glucose Homeostasis in Female Aromatase Knockout Mice
The effects of estrogens on glucose homeostasis in female ArKO mice are described and a primary phenotype of hepatic glucose dysregulation and a parallel estrogen modified adipokine profile is highlighted. Expand
Beneficial effects of tibolone on blood pressure and liver redox status in ovariectomized rats with renovascular hypertension.
In the liver, although exerting an undesirable inhibition of mitochondrial and peroxisomal β-oxidation, tibolone reversed steatosis and improved the liver redox status and reversed the main alterations caused by hypertension and estrogen deficiency. Expand
Impact of Obesity on Mammary Gland Inflammation and Local Estrogen Production
  • K. Brown
  • Medicine
  • Journal of Mammary Gland Biology and Neoplasia
  • 2014
This review will explore the relationship between obesity, inflammation and estrogens, with a particular focus on the molecular regulation of aromatase in the postmenopausal breast in the context of obesity and breast cancer. Expand
Obesity and Breast Cancer


Estrogen and adiposity—Utilizing models of aromatase deficiency to explore the relationship
It is demonstrated that an increased androgen to estrogen ratio can promote visceral fat accumulation in the rodent by inhibiting AMPK activation and stimulating lipogenesis. Expand
Tibolone: a steroid with a tissue-specific mode of action
  • H. Kloosterboer
  • Medicine, Biology
  • The Journal of Steroid Biochemistry and Molecular Biology
  • 2001
It is concluded that tibolone acts as a tissue-specific compound by mediating its effects via steroid receptors and enzymatic pathways, and avoids stimulation of the endometrium and breast tissue. Expand
Aromatase-deficient (ArKO) mice have a phenotype of increased adiposity.
An important role for estrogen in the maintenance of lipid homeostasis in both males and females is demonstrated, reflected in increased adipocyte volume at gonadal and infrarenal sites. Expand
Cellular and molecular characterization of the adipose phenotype of the aromatase-deficient mouse.
Estrogen deficiency in the aromatase knockout (ArKO) mouse leads to the development of obesity by as early as 3 months of age, which is characterized by a marked increase in the weights of gonadalExpand
Tibolone : A Selective Tissue Estrogenic Activity Regulator
Tibolone is a STEAR (Selective tissue estrogenic activity regulator) (1). It is a synthetic steroid with tissue selectivity that has progestogenic, some androgenic as well as estrogenic effects. ItExpand
Aromatase-deficient (ArKO) mice accumulate excess adipose tissue
An important role for estrogen in the maintenance of lipid homeostasis in both males and females is demonstrated, and the consequences of estrogen deficiency on accumulation of adipose depots in male and female ArKO mice are examined. Expand
Molecular portrait of the progestagenic and estrogenic actions of tibolone: behavior of cellular networks in response to tibolone.
The final genetic network analysis indicated that the estrogenic effect of tibolone is potentially counterbalanced by the progestagenic metabolite of tIBolone via differential regulation of similar cellular processes. Expand
Tibolone and its metabolites: Pharmacology, tissue specificity and effects in animal models of tumors
Tibolone is a steroid with weak estrogenic, progestogenic and androgenic properties that can be used as an alternative to conventional hormone replacement therapy in postmenopausal women. Tibolone isExpand
Of mice and men: the evolving phenotype of aromatase deficiency
By studying the naturally occurring aromatase-deficient humans, together with studies of the arom atase-knockout mouse, the understanding of the essential role of estrogen in male physiology is expanded. Expand
The aromatase knockout mouse presents with a sexually dimorphic disruption to cholesterol homeostasis.
A sexually dimorphic difference in mouse hepatic cholesterol homeostasis and roles for estrogen in the regulation of cholesterol uptake, biosynthesis, and catabolism in the female, but not in the male are revealed. Expand