ABSTRACT Evidence from knockout studies in male mice and from experiments in male rats,in which expression of the estrogen receptor alpha (ERα) gene was inhibited in the medial preoptic area (MPO), suggests that ERα is important in the control of male rat mating behavior. Therefore, in this experiment, we tested the hypothesis that activation of ERα in the MPO is sufficient to maintain mating behavior in castrated male rats receiving subcutaneously (s.c.) dihydrotestosterone (DHT), a non-aromatizable androgen. Accordingly, castrated rats treated with DHT s.c. received MPO implants of either: (i) propyl-pyrazole-triol (PPT) (Stauffer, et al 2000; Katzenellenbogen, et al 2000), a selective ERα agonist, (ii) E2 (positive controls) or (iii) cholesterol (negative controls)and sexual behavior was monitored. PPT was as effective as E2 at maintaining mating behavior suggesting that, in the MPO, ERα is sufficient to mediate responses to E2 that underlie male rat mating behavior.

Estrogen stimulation of the medial amygdala (MEA) of the brain promotes male rat mating behavior. However, selective stimulation of either of the estrogen receptor subtypes found in the MEA (ERα or ERβ) does not support mating behavior. We tested the hypothesis that dual stimulation of ERα and ERβ is required to activate estrogen-dependant neural circuits in the MEA responsible for mating by local treatment of MEA with a combination of selective estrogenic agonists: propyl pyrazole triol (PPT, an ERα agonist ) and diarylpropionitrile (DPN, an ERβ agonist) administered to castrated, DHT maintained male rats. Estradiol (E2) or cholesterol (Chol) MEA implants served as positive and negative controls respectively. The animals receiving a mixture of PPT and DPN into the MEA displayed higher levels of mating behavior than the Chol treated animals but lower levels of mating behavior than the E2 treated animals.