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Estrogen receptor (ER) α is involved in several estrogen-modulated neural and peripheral functions. To determine its role in the expression of female and male reproductive behavior, a mouse line lacking the  ERα  in the nervous system was generated. Mutant females did not exhibit sexual behavior despite normal olfactory preference, and had a reduced number of progesterone receptor-immunoreactive neurons in the ventromedial hypothalamus. Mutant males displayed a moderately impaired sexual behavior and unaffected fertility, despite evidences of altered organization of sexually dimorphic populations in the preoptic area. In comparison, males deleted for both neural  ERα  and androgen receptor ( AR ) displayed greater sexual deficiencies. Thus, these data highlight a predominant role for neural  ERα  in females and a complementary role with the AR in males in the regulation of sexual behavior, and provide a solid background for future analyses of neuronal versus glial implication of these signaling pathways in both sexes.

Deletion of neural estrogen receptor alpha induces sex differential effects on reproductive behavior in mice