Medroxyprogesterone acetate and the nuclear uptake of testosterone and its metabolites by brain, pituitary gland and genital tract in male cynomolgus monkeys.
The synthetic progestin, medroxyprogesterone acetate (MPA), is used to treat male sex offenders, and it is also suppresses sexual activity in male monkeys. To examine the possibility that MPA may act as an anti-androgen in the primate brain, 4 intact male cynomolgus monkeys were given MPA (40 mg i.m.) once a week for 16 weeks, while 4 control males received i.m. injections of vehicle. All males were then castrated and 3 days later were given 3 mCi [3H]testosterone ([3H]T) i.v.; 1 h after injection males were killed, and radioactivity in nuclear pellets obtained from the hypothalamus (HYP), preoptic area (POA), amygdala (AMG), septum, pituitary gland and genital tract was analyzed by HPLC. Concentrations of [3H]T and [3H]dihydrotestosterone in nuclear pellets were 65-96% lower in MPA-treated males than in controls (P less than 0.001), but the aromatized metabolite, [3H]estradiol, which was the major form of radioactivity present in nuclear pellets from HYP, POA and AMG, was unchanged. There were no differences in concentrations of [3H]T in supernatants from the tissues of MPA-treated and control males. Because the reduced nuclear uptake of androgen in brain occurred in males whose androgen-dependent behavior had been suppressed by MPA treatments, it is proposed that MPA may have anti-androgenic effects at the level of the cell nucleus in brain regions that control behavior.
Michael
R P
RP
Department of Psychiatry, Emory University School of Medicine, Atlanta, GA 30322.
Bonsall
R W
RW
Zumpe
D
D
D000818:Animals; D001921:Brain / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism*; D005837:Genitalia, Male / Q000033:anatomy & histology / Q000378:metabolism; D008252:Macaca fascicularis; D008297:Male; D008525:Medroxyprogesterone / Q000031:analogs & derivatives* / Q000378:metabolism; D017258:Medroxyprogesterone Acetate; D009929:Organ Size / Q000187:drug effects; D010902:Pituitary Gland / Q000378:metabolism; D012726:Sexual Behavior, Animal / Q000187:drug effects / Q000502:physiology; D013739:Testosterone / Q000378:metabolism* / Q000493:pharmacokinetics
D013739:Testosterone; D017258:Medroxyprogesterone Acetate; D008525:Medroxyprogesterone