Suppression of bioactive luteinizing hormone and testosterone by a progesterone antagonist ZK 98.734 in adult male common marmosets, Callithrix jacchus.
The effects of a progesterone antagonist ZK 98.734 on release of bioactive luteinizing hormone (LH) and testosterone were studied in adult male common marmosets by using the following experimental protocols: (1) the blocking of the nocturnal rise in testosterone levels by ZK 98.734, (2) the pharmacodynamic effects of ZK 98.734 on testosterone and LH levels, (3) the reversal of ZK 98.734-induced decrease in testosterone by treatment with human chorionic gonadotropin (hCG), and (4) the blocking of estradiol-induced positive feedback release of LH by ZK 98.734. Sixteen adult male common marmosets were used for different experiments after resting them for at least 4 wk between experiments. Testosterone and bioactive LH levels were measured by specific radioimmunoassay and in vitro bioassay methods, respectively. Treatment (i.m.) of male common marmosets (n = 6/group) with ZK 98.734 (1 mg or 5 mg/day) at 1700 h for 3 consecutive days significantly (p less than 0.05) suppressed the nocturnal (2200 h) rise in testosterone levels. The effects of the two doses were not dose-related; however, the decrease on the first day of treatment was more pronounced with the 5-mg dose than with the 1-mg dose. Diurnal rhythms were restored during the post-treatment period. Similarly, treatment with ZK 98.734 (5 mg, n = 8/group) at 1000 h caused a decrease in testosterone and LH levels. The levels were significantly (p less than 0.05) lower at 3 and 6 h after treatment compared to pretreatment levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Kholkute
S D
SD
Institute for Research in Reproduction (ICMR)3 Parel, Bombay, India.
Patil
R K
RK
Sharma
S
S
Elger
W A
WA
Puri
C P
CP
D000818:Animals; D002143:Callitrichinae; D002940:Circadian Rhythm; D004958:Estradiol / Q000494:pharmacology; D004963:Estrenes / Q000494:pharmacology*; D007700:Kinetics; D007986:Luteinizing Hormone / Q000097:blood / Q000378:metabolism*; D008297:Male; D011374:Progesterone / Q000037:antagonists & inhibitors*; D012016:Reference Values; D013739:Testosterone / Q000097:blood / Q000378:metabolism*
D004963:Estrenes; C048260:lilopristone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol; D007986:Luteinizing Hormone