Molecular Endocrinology, Vol 7, 597-603, Copyright © 1993 by Endocrine Society

ARTICLES

Transactivation and synergistic properties of the mineralocorticoid receptor: relationship to the glucocorticoid receptor

R Rupprecht, JL Arriza, D Spengler, JM Reul, RM Evans, F Holsboer and K Damm
Department of Neuroendocrinology, Max Planck Institute of Psychiatry, Munich, Germany.

The human mineralocorticoid (hMR) and glucocorticoid (hGR) receptors mediate biological responses to adrenal corticosteroids and synthetic ligands. In transient transfection studies, corticosteroid-responsive promoters were used to monitor the hormone-dependent transcriptional regulatory properties of both receptors. The hMR mediates a lower stimulation of the transcription rate than the hGR and does not show cooperative activity on promoters containing multiple palindromic glucocorticoid-responsive elements. The functional importance of the amino-terminus in this differential response was demonstrated by hMR/hGR hybrid receptors in which this region was exchanged or deleted. These experiments revealed that the hMR amino-terminus does not provide the strong transactivation function present in the equivalent hGR domain and, in contrast to the hGR amino-terminus, interferes with the synergistic activity mediated by the DNA- and ligand-binding domains of both receptors.

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