The antagonists RU486 and ZK98299 stimulate progesterone receptor binding to deoxyribonucleic acid in vitro and in vivo, but have distinct effects on receptor conformation

Endocrinology
E K GassD P Edwards

Abstract

Three types of transfection experiments were used to detect the abilities of different classes of antagonists to stimulate binding of progesterone receptor (PR) to progesterone response elements (PRE) in intact mammalian cells. These included a promoter interference assay, in which PR binding to PREs positioned between the TATA box and the start of transcription is detected as a reduction of expression of a constitutively active reporter gene, competition of PR antagonist and glucocorticoid receptor agonist for a common glucocorticoid response element/PRE-controlled reporter construct, and activation of a chimeric receptor (PR-VP16) containing the constitutive trans-activation domain derived from the VP16 protein of herpes simplex virus. By each approach, all antagonists tested were equally effective in stimulating PR binding to PREs in the cell. This included previously designated type I (ZK98299) and type II (RU486, ZK98734, and ZK112993) 11beta-aryl substituted steroid analogs. Stimulation of PR binding to PREs in the cell by ZK98299 was of interest because this antagonist has been reported to lack the ability to stimulate PR-DNA binding in vitro by electrophoretic gel mobility shift assay compared with RU486, which promotes...Continue Reading

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Citations

Jun 6, 2002·Proceedings of the National Academy of Sciences of the United States of America·Zheng LiuBert W O'Malley
Jul 9, 2002·Molecular and Cellular Biology·Suzanne E WardellDean P Edwards
Mar 4, 2005·Molecular and Cellular Biology·Geetha V RayasamGordon L Hager
Dec 15, 2015·Molecular Endocrinology·Lindsey S TreviñoNancy L Weigel
Feb 18, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Dec 18, 2002·Experimental Biology and Medicine·Susan A Leonhardt, Dean P Edwards
Feb 25, 2005·The Journal of Biological Chemistry·Ze-Yi ZhengValerie C-L Lin

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