The FORKO mouse as a genetic model for exploring estrogen replacement therapy.

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.