Effect of 5 alpha-dihydrotestosterone on sexual receptivity and neural progestin receptors in ovariectomized rats given pulsed estradiol.
Experiments were carried out to examine the mechanism whereby 5 alpha-dihydrotestosterone (DHT) antagonizes the stimulatory effects of estrogen plus progesterone (P) on sexual receptivity (lordosis) in the ovariectomized rat. Estradiol (E2; 1 microgram s.c. in 10% ethanol) was administered in a discontinuous (pulsed) treatment regimen thought to mimic phase requirements of estrogen action; two injections of E2 were given either 6 or 12 h apart (first injection, Hour 0). Progesterone (0.5 mg in oil) was injected at Hour 20, and behavioral testing occurred at Hour 24. Dihydrotestosterone (2.5 mg s.c. in 10% ethanol/propylene glycol) inhibited lordosis when it was given before (-12 or -3 h), between (+3, or -3 and +3 h), or after (+8 h) the two E2 injections, but was not effective when given at +20 h. Significant inhibition of E2 + P-induced lordosis was achieved by 2.5 but not 1.0 or 0.2 mg DHT at -3 h, while uterine weights in the same animals were reduced significantly by 2.5 and 1.0 mg DHT. Serum E2 and DHT concentrations peaked rapidly after injection, declining to near baseline by 3 and 12 h, respectively. Induction of cytosolic progestin receptors (cPR) in the preoptic area and medial basal hypothalamus by estrogen was not prevented by DHT when animals were given the two pulsed E2 injections or daily injections of estradiol benzoate, although P was able to override the inhibitory behavioral effects of DHT in the latter but not the former group.(ABSTRACT TRUNCATED AT 250 WORDS)
D000818:Animals; D003600:Cytosol / Q000187:drug effects; D013196:Dihydrotestosterone / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004958:Estradiol / Q000097:blood / Q000494:pharmacology*; D005260:Female; D007031:Hypothalamus / Q000187:drug effects*; D007033:Hypothalamus, Middle / Q000187:drug effects; D010052:Ovariectomy; D011301:Preoptic Area / Q000187:drug effects; D011374:Progesterone / Q000494:pharmacology; D051381:Rats; D011980:Receptors, Progesterone / Q000187:drug effects*; D012726:Sexual Behavior, Animal / Q000187:drug effects*
D011980:Receptors, Progesterone; D013196:Dihydrotestosterone; D011374:Progesterone; D004958:Estradiol; C030445:dihydrotestosterone propionate