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Review
. 1996;70(3):183-213.
doi: 10.1016/0163-7258(96)00016-2.

The antiglucocorticoid action of mifepristone

Affiliations
Review

The antiglucocorticoid action of mifepristone

M K Agarwai. Pharmacol Ther. 1996.

Abstract

Glucocorticoid hormones influence the physiological activity of almost all cell types in the mammal. This is accomplished via a soluble receptor that, in the presence of an appropriate steroid, modifies the activity of RNA polymerase by binding to the site where different factors assemble for the initiation of cell transcription. The development of antiglucocorticoids has permitted the molecular elucidation of a number of underlying events. Contrary to the classical view, it is now clear that the affinity, stability and activability of the glucocorticoid receptor in the presence of a steroid are cell- and/or tissue-dependent events. The antiglucocorticoid RU 38486 can even activate transcription by binding to sites distinct from those that process transactivation by the agonist. Furthermore, glucocorticoids can sometimes activate the mineralocorticoid receptor, whereas mineralocorticoids can bind the glucocorticoid receptor. Since mifepristone is devoid of adverse toxicity, it has been used for the paraclinical diagnosis of the hypothalamus-pituitary-adrenal axis in normal volunteers, subjects with disorders of the behaviour, and the treatment of Cushing's disease. However, the whole spectrum of cell-specific processes that are antagonized by RU 38486 suggests wide ranging possibilities in the eventual application of antigluco-corticoids.

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