RU486 Reversal of Cortisol Repression of 1,25-Dihydroxyvitamin D₃ Induction of the Human Osteocalcin Promoter

Nigel A. Morrison

School of Medical Science, Griffith University, Gold Coast Campus, Gold Coast, Australia.

DOI: 10.4236/ojemd.2013.31009                

Abstract

In conditions of corticosteroid excess, such as Cushing’s syndrome, a reduction in serum osteocalcin is observed and bone loss occurs. The human osteocalcin gene is induced by 1,25-dihydroxyvitamin D₃ derivatives and repressed by glucocorticoids. In this paper we show that cortisol, a natural glucocorticoid, represses both basal and vitamin D induced activity of the human osteocalcin promoter. Furthermore, we address the specific question as to whether the anti-progestin anti-glucocorticoid RU486 is able to antagonize the inhibitory effect of cortisol on osteocalcin gene expression. We show that RU486 has agonist activity alone, in that it is able to repress the basal promoter activity of the osteocalcin gene and antagonist activity, reversing incompletely the cortisol mediated repression of 1,25-dihydroxyvitamin D3 induction.

Keywords

RU486; Osteocalcin; Vitamin D; Glucocorticoid

Conflicts of Interest

The authors declare no conflicts of interest.

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