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

TLDR

The human mineralocorticoid (hMR) and glucocorticoid (hGR) receptors mediate biological responses to adrenal corticosteroids and synthetic ligands. Transient transfection with corticosteroid‑responsive promoters was used to assess hormone‑dependent transcription of hMR and hGR, and swapping or deleting the amino‑terminus in hybrid receptors demonstrated its role in differential transactivation. hMR shows weaker transcriptional activation than hGR, lacks cooperative activity on promoters with multiple glucocorticoid‑responsive elements, and its amino‑terminus fails to provide strong transactivation while interfering with synergistic activity mediated by the DNA‑ and ligand‑binding domains.

Abstract

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.