Role of tissue-specific steroid metabolism in oral disease: Is there any clinical implication?

The discovery of an oral glucocorticoid system has provided novel conceptual frameworks for understanding the effects of endogenous and exogenous corticosteroids in the oral cavity. For example, liquorice derivatives have long been used in the treatment of oral inflammatory conditions and it is now known that a chief constituent of liquorice root, glycyrrhetinic acid, inhibits 11β-hydroxysteroid dehydrogenase (11β-HSD) type 2 thus increasing local cortisol levels. Hence, targeting the local interconversion between inactive cortisone and active cortisol by 11β-HSD inhibitors/activators offers potentially advantageous strategies for the treatment of oral inflammatory and autoimmune conditions. The recent characterisation of a cancer-associated glucocorticoid system has further extended the implications of cortisol metabolism in oral disease. New evidence now questions the use of synthetic corticosteroids in patients with cancer and, possibly, in oral potentially malignant disorders. For example, cortisol production by cancer cells has been shown to inhibit tumour-specific CD8⁺ T cells, to promote migration and invasion and to induce chemoresistance in vitro. This viewpoint briefly summarises the recent evidence for a role of the local steroid metabolism in oral oncology and immunology and its potential clinical implications.