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The FORKO mouse as a genetic model for exploring estrogen replacement therapy
M Ram Sairam1, Natalia Danilovich, Suzanne Lussier-Cacan
1Molecular Reproduction Research Laboratory, Clinical Research Institute of Montreal, 110 Pine Avenue West, Montreal, Quebec, H2W 1R7, Canada. sairamm@ircm.qc.ca
Objective:
To evaluate how chronically estrogen deficient female FORKO mice with genetic disruption of the FSH receptor respond to estrogen therapy.
Study Design:
Subcutaneous estrogen agonist or antagonist therapy was initiated to study reproductive tissue response, adipose tissue mass and plasma lipid profiles.
Results:
Within 36-48 hours of agonist administration, the classic measures of estrogenic activity were evident in the uterus and vagina. Older animals also responded to therapy during a 10-day period, indicating that estrogen receptor signaling systems are unaffected by aging. In these obese mutants, this short treatment decreased adipose tissue in all areas and corrected lipid abnormalities. Tamoxifen, a nonsteroidal mixed estrogen agonist and antagonist, had marginal effects on the uterus and body fat of FORKO mice, indicating differences in interaction.
Conclusion:
In FORKO mice lacking ovarian estrogen, the receptors remain fully functional. Hence, this is a useful model for studying estrogen replacement therapy and helps resolve questions related to efficacy and actions.