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Estrogen receptor function as revealed by knockout studies: neuroendocrine and behavioral aspects
E F Rissman1, S R Wersinger, J A Taylor
1Department of Biology, University of Virginia, Charlottesville 22903, USA. efr2f@virginia.edu
Hormones and Behavior
|June 1, 1997
Summary
Estrogen receptor alpha (ER alpha) is crucial for regulating reproductive hormones and sexual behaviors in mice. ER alpha disruption significantly impacts neuroendocrine function and behavior in both males and females.
Area of Science:
- Endocrinology
- Neuroscience
- Behavioral Biology
Background:
- Estrogens are vital steroid hormones influencing tissue development and physiological functions.
- The discovery of multiple estrogen receptors (ER beta, ER alpha variants, membrane receptors) necessitates tools to differentiate ER alpha's specific roles.
- Understanding ER alpha function is key to deciphering estrogenic effects on behavior and neuroendocrinology.
Purpose of the Study:
- To investigate the specific role of the estrogen receptor alpha (ER alpha) protein in behavior and neuroendocrine function.
- To utilize ER alpha-null mice to distinguish estrogenic effects mediated by ER alpha from those mediated by other estrogen receptors.
- To elucidate the direct and indirect functions of ER alpha in regulating reproductive axes and behaviors.
Main Methods:
- Generation and analysis of mice lacking functional estrogen receptor alpha (ER alpha-null mice).
- Comparison of hormonal profiles (estradiol, testosterone, luteinizing hormone) between wild-type and ER alpha-null mice.
- Assessment of sexual receptivity in ovariectomized female ER alpha-null mice treated with estrogen and progesterone.
- Evaluation of male sexual behaviors in ER alpha-null animals.
Main Results:
- ER alpha is essential for the normal regulation of the hypothalamic-pituitary gonadal axis in female mice.
- ER alpha-null female mice fail to display sexual receptivity under hormonal stimulation that induces it in wild-type mice.
- Disruption of ER alpha function leads to significant impairments in male sexual behaviors.
Conclusions:
- Estrogen receptor alpha plays a critical and direct role in mediating female sexual receptivity and regulating the reproductive axis.
- ER alpha is indispensable for normal sexual behavior in both male and female mice.
- ER alpha-null mice provide a valuable model for dissecting the specific functions of ER alpha and exploring the roles of other estrogen receptors.