Behavioral responses to Depo-Provera, Fadrozole, and estradiol in castrated, testosterone-treated cynomolgus monkeys (Macaca fascicularis): the involvement of progestin receptors.
Sexual motivation and behavior decreased in male cynomolgus monkeys given either Depo-Provera (medroxyprogesterone acetate, MPA), which reduces androgen uptake by brain, or the nonsteroidal aromatase inhibitor, Fadrozole, which virtually eliminates the conversion of testosterone (T) to estradiol (E2) in brain. This suggested that both unchanged T and E2 are important for the control of male primate sexual behavior, but combined treatment with MPA and Fadrozole did not have the anticipated summatory effects in intact males: the behavioral decrements when MPA-treated males were given Fadrozole were about half those observed when Fadrozole was given alone. The present study tested the hypothesis that Fadrozole suppressed the behavioral effects of MPA by preventing the induction by E2 of progestin receptors in the brain to which MPA binds. Eight castrated, T-treated males were each tested with an estrogenized female i) during baseline, ii) during MPA treatment, iii) during treatment with MPA and Fadrozole together, and iv) with E2 treatment added to condition (iii) (256 1-h behavior tests). All dosages were those used in previous studies. Sexual motivation, as reflected in mounting attempts and mounting attempt latencies, was further diminished by E2 treatment in males receiving both MPA and Fadrozole, but ejaculatory activity was not changed. Immunocytochemistry demonstrated that the distributions of progestin and androgen receptors were little affected by MPA treatment, and that progestin receptor immunoreactivity was almost completely abolished in the brains of males receiving both MPA and Fadrozole but present in those receiving additional E2 treatment, findings that supported the hypothesis.
Zumpe
D
D
Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA 30322, USA.
Clancy
A N
AN
Bonsall
R W
RW
Michael
R P
RP
D000818:Animals; D047072:Aromatase Inhibitors; D001923:Brain Chemistry / Q000187:drug effects; D004542:Ejaculation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004958:Estradiol / Q000494:pharmacology*; D017316:Fadrozole / Q000494:pharmacology*; D005260:Female; D008252:Macaca fascicularis; D008297:Male; D017258:Medroxyprogesterone Acetate / Q000494:pharmacology*; D009919:Orchiectomy; D010052:Ovariectomy; D045167:Progesterone Congeners / Q000494:pharmacology*; D011944:Receptors, Androgen / Q000187:drug effects / Q000378:metabolism; D011980:Receptors, Progesterone / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects; D013739:Testosterone / Q000494:pharmacology*; D015000:Yawning / Q000187:drug effects
D047072:Aromatase Inhibitors; D004791:Enzyme Inhibitors; D045167:Progesterone Congeners; D011944:Receptors, Androgen; D011980:Receptors, Progesterone; D013739:Testosterone; D004958:Estradiol; D017258:Medroxyprogesterone Acetate; D017316:Fadrozole