Document Detail


Effects of progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of nidation, and termination of pregnancy in bonnet monkeys.
MedLine Citation:
PMID:  2271724     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The effects of a progesterone antagonist, lilopristone (ZK 98.734), on induction of menstruation, inhibition of implantation or pregnancy, and termination of early and mid-pregnancy were studied in bonnet monkeys. In the regularly menstruating animals, administration of lilopristone (25 mg/day, s.c.) during the mid-luteal phase (Days 20-22 of the menstrual cycle) induced menstruation within 2-4 days after the initiation of treatment. A premature drop in circulating progesterone levels was also observed. The luteolytic effect of lilopristone was prevented by exogenous treatment with hCG; however, the animals showed premature menstruation, in spite of high progesterone levels (above 4 ng/ml). Treatment around the time of implantation (between Days 8 and 12 after the mid-cycle peak in estradiol levels) in mated animals provided 100% pregnancy protection. Treatment of pregnant animals on Days 30-32 of the menstrual cycle, i.e. about Day 20 after the estradiol peak, induced abortion in 8 of 10 animals. A significant (p less than 0.05) decrease in serum progesterone levels was observed on Day 3 after the initiation of treatment. However, the decrease was slower (slope: -0.36, r: 0.96) compared to that observed in nonpregnant animals (slope: -0.72, r: 0.95). In the other two animals, pregnancy was not affected. However, when the treatment was delayed until about Day 50 after the estradiol peak, all four animals aborted. This study suggests that lilopristone is a progesterone antagonist with a potential to induce menstruation, inhibit nidation, and terminate pregnancy. The antifertility effects are mediated through blocking progesterone action at the endometrium as well as decreasing progesterone bioavailability, which appears to be due to its effects on gonadotropin release.
Authors:
C P Puri; R R Katkam; A D'Souza; W A Elger; R K Patil
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biology of reproduction     Volume:  43     ISSN:  0006-3363     ISO Abbreviation:  Biol. Reprod.     Publication Date:  1990 Sep 
Date Detail:
Created Date:  1991-02-25     Completed Date:  1991-02-25     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0207224     Medline TA:  Biol Reprod     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  437-43     Citation Subset:  IM    
Affiliation:
Institute for Research in Reproduction (ICMR), Parel, Bombay, India.
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MeSH Terms
Descriptor/Qualifier:
Animals
Chorionic Gonadotropin / pharmacology
Embryo Implantation / drug effects*
Estradiol / metabolism
Estrenes / pharmacology*
Female
Macaca radiata
Menstruation / drug effects*,  metabolism
Pregnancy / drug effects*
Progesterone / blood
Progestins / antagonists & inhibitors
Chemical
Reg. No./Substance:
0/Chorionic Gonadotropin; 0/Estrenes; 0/Progestins; 50-28-2/Estradiol; 57-83-0/Progesterone; 97747-88-1/lilopristone
Comments/Corrections
Erratum In:
Biol Reprod 1990 Oct;43(4):following 717

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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