Sexual dimorphism in the glucose homeostasis phenotype of the Aromatase Knockout (ArKO) mice

Document Type

Journal Article

Publication Title

The Journal of Steroid Biochemistry and Molecular Biology


Elsevier Ltd


School of Medical and Health Sciences




Van Sinderen, M., Steinberg, G., Jorgensen, S. B., Honeyman, J., Chow, J. D., Simpson, E. R., . . . Boon, W. C. (2017). Sexual dimorphism in the glucose homeostasis phenotype of the Aromatase Knockout (ArKO) mice. The Journal of steroid biochemistry and molecular biology, 170, 39-48.


We investigated the effects of estrogens on glucose homeostasis using the Aromatase Knockout (ArKO) mouse, which is unable to convert androgens into estrogens. The ArKO mouse is a model of total estrogen ablation which develops symptoms of metabolic syndrome.

To determine the development and progression of whole body state of insulin resistance of ArKO mice, comprehensive whole body tolerance tests were performed on WT, ArKO and estrogen administrated mice at 3 and 12 months of age. The absence of estrogens in the male ArKO mice leads to hepatic insulin resistance, glucose and pyruvate intolerance from 3 to 12 months with consistent improvement upon estrogen treatment. Estrogen absence in the female ArKO mice leads to glucose intolerance without pyruvate intolerance or insulin resistance. The replacement of estrogens in the female WT and ArKO mice exhibited both insulin sensitizing and resistance effects depending on age and dosage.

In conclusion, this study presents information on the sexually dimorphic roles of estrogens on glucose homeostasis regulation.



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