Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands.

Article Details

Citation

Copy to clipboard

Rupprecht R, Reul JM, van Steensel B, Spengler D, Soder M, Berning B, Holsboer F, Damm K

Pharmacological and functional characterization of human mineralocorticoid and glucocorticoid receptor ligands.

Eur J Pharmacol. 1993 Oct 15;247(2):145-54.

PubMed ID

8282004 [ View in PubMed

]

Abstract

We characterized the pharmacological profiles of the human mineralocorticoid and glucocorticoid receptor for 11 natural and synthetic steroids regarding binding pharmacology, intracellular localization of hormone-receptor complexes, and agonistic or antagonistic properties at the gene expression level. The sex steroid progesterone bound with an affinity (ki < 0.01 nM) even higher than that of aldosterone to the human mineralocorticoid receptor and effectively antagonized the effect of aldosterone via the human mineralocorticoid receptor in functional co-transfection assays. This indicates that progesterone has potent antimineralocorticoid properties, while its antiglucocorticoid effects were less pronounced. The partial agonistic activities of antihormones in this assay suggest a direct interaction of antihormone-receptor complexes with the response elements on the DNA. These results are supported by immunofluorescence studies, in which both unliganded human mineralocorticoid and glucocorticoid receptors were distributed throughout the cytoplasm and nucleus, whereas agonist- as well as antagonist-receptor complexes showed an exclusively nuclear localization. These results contribute to the understanding of antihormone pharmacology and increase our understanding of the role of human mineralocorticoid and glucocorticoid receptors in physiological processes during different endocrine states.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
Progesterone	Mineralocorticoid receptor	Protein	Humans	Yes	Antagonist Agonist	Details