Document Detail


The blockade of mineralocorticoid hormone signaling provokes dramatic teratogenesis in cultured rat embryos.
MedLine Citation:
PMID:  12055020     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although the administration of adrenocortical hormones to pregnant rats provokes only limited effect on the growth and development of the fetus, the direct influence of these steroids on cultured embryos has never been studied. The disruption of cell signaling by ZK 91587, which specifically occupies the mineralocorticoid receptor, resulted within 2 days in significant and pronounced adverse effects on the total length, the somite number, the embryo curvature, the communication between vitelline and umbilical blood vessels in the allantoid, and the vascularization of the vitelline sac, in 244-hour Wistar rat embryos in culture. The average score of 16 organs declined in a dose-dependent manner, following exposure to ZK 91587, and this was totally reversed by 10 microM aldosterone which, by itself, did not at all influence the embryonic development. The organogenesis was inhibited in the order: hind limb > fore limb > optic stalk > brain > olfactory pit > otic vesicle. ZK 91587 was completely ineffective in embryos that had attained the age of 260 hours. Similar, but less dramatic, results were obtained with the mineralocorticoid antagonist RU 26752, and with the antiglucocorticoid RU 38486. Sprague-Dawley rat embryos responded in a manner similar to the Wistar conceptuses. Thus, steroid receptor-mediated cell signaling is of critical importance to the growth and development of cultured rat embryos, which form a new model system to unravel adrenocortical hormone action.
Authors:
M Mirshahi; E Ayani; C Nicolas; N Golestaneh; P Ferrari; F Valamanesh; M K Agarwal
Publication Detail:
Type:  In Vitro; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  International journal of toxicology     Volume:  21     ISSN:  1091-5818     ISO Abbreviation:  Int. J. Toxicol.     Publication Date:    2002 May-Jun
Date Detail:
Created Date:  2002-06-10     Completed Date:  2002-12-30     Revised Date:  2007-11-15    
Medline Journal Info:
Nlm Unique ID:  9708436     Medline TA:  Int J Toxicol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  191-9     Citation Subset:  IM    
Affiliation:
INSERM, Faculté de Médecine Paris VI, Paris, France. massoud.mirshani@bhdc.jussieu.fr
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MeSH Terms
Descriptor/Qualifier:
Animals
Dose-Response Relationship, Drug
Embryo, Mammalian / drug effects*
Epithelial Sodium Channel
Female
Immunohistochemistry
Male
Mifepristone / toxicity
Mineralocorticoids / antagonists & inhibitors*
Organ Culture Techniques
Polymerase Chain Reaction
Pregnancy
RNA, Messenger / analysis
Rats
Receptors, Mineralocorticoid / biosynthesis*
Signal Transduction / drug effects*
Sodium Channels / biosynthesis*
Spironolactone / analogs & derivatives*,  toxicity
Teratogens / toxicity*
Chemical
Reg. No./Substance:
0/Epithelial Sodium Channel; 0/Mineralocorticoids; 0/RNA, Messenger; 0/Receptors, Mineralocorticoid; 0/Sodium Channels; 0/Teratogens; 52-01-7/Spironolactone; 76676-33-0/7-propyl spirolactone; 84371-65-3/Mifepristone; 84542-26-7/ZK 91587

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


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