Nonaromatizable androgens may stimulate a male mouse reproductive behavior by binding estrogen receptors.

Castrated DBA/2J male mice emitted 70 kHz vocalizations to female stimuli in response to 10 days of treatment with either testosterone (T, 300 micrograms/day), diethylstilbestrol (DES, 1 or 3 micrograms/day) or methyltrienolone (R1881, 900 micrograms/day). Lower dosages of R1881 (300 and 600 micrograms/day) and the oil vehicle were relatively ineffective in restoring vocalizations. The effects of these hormones on restoring seminal vesicle weight did not always parallel their effects upon behavior. In general T and R1881 (600 and 900 micrograms/day) were effective in restoring seminal vesicles while DES, the lowest dose of R1881 (300 micrograms/day), and the oil vehicle were ineffective. In receptor competition studies, R1881 pretreatment significantly reduced estrogen binding in hypothalamic-preoptic cytosol. In fact the most effective dose for restoring vocalizations (900 micrograms/day) reduced available estrogen binding sites by 91%. We propose that the male-typical vocalizations of mice may normally be stimulated through the activation of estrogen receptors following androgen aromatization and that the ability of a pharmacological dosage of R1881 (900 micrograms/day) to restore behavior may be due to interaction with estrogen receptors in the brain.