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11β-hydroxysteroid dehydrogenase type I in the brain; thickening the glucocorticoid soup

Molecular Psychiatry volume 6, pages 611–614 (2001)Cite this article

Glucocorticoids are secreted from the adrenal cortex in response to diurnal cues and stress. They affect a wide range of processes in the brain, altering neurotransmission, electrophysiological activity, cellular metabolism and structure, as well as neuronal division, maturation and death. Acute elevation of glucocorticoid levels is typically adaptive to stress, facilitating beneficial responses such as fear conditioning. In contrast, chronic glucocorticoid excess (eg in Cushing's syndrome) exerts profound adverse effects on the brain, producing neuropsychiatric dysfunction (depression, psychosis) cognitive impairments, structural changes and neuroendocrine dysfunction. Such effects are underpinned by altered neuronal metabolism, electrical activity and the pruning of dendritic structure in the hippocampus, a region especially sensitive to glucocorticoids.1 Clearly, maintaining glucocorticoid actions within close limits of tolerance is important for health. Aging is associated with both a tendency towards elevation of blood glucocorticoid levels and increased neuronal sensitivity to the adverse effects of glucocorticoids.2

It has been a long accepted tenet that glucocorticoid actions are determined solely by the concentration of hormone in the circulation (modulated by hormone binding to plasma proteins) and by the density of intracellular receptors in target tissues. Recently however, it has become apparent that enzymic pre-receptor metabolism of glucocorticoids by 11β-hydroxysteroid dehydrogenase (11β-HSD) also potently regulates steroid access to receptors within specific tissues. The broader physiological importance of this novel level of regulation is emerging from studies in knockout mice.

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Acknowledgements

Work in the authors’ laboratory was supported by a Programme grant from the Wellcome Trust and a Wellcome Trust Senior Clinical Fellowship (JRS).

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  1. Endrocrinology Unit, Molecular Medicine Centre, Western General Hospital, Edinburgh, EH4 2XU, UK

    J L W Yau & J R Seckl

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  1. J L W Yau
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Yau, J., Seckl, J. 11β-hydroxysteroid dehydrogenase type I in the brain; thickening the glucocorticoid soup. Mol Psychiatry 6, 611–614 (2001). https://doi.org/10.1038/sj.mp.4000967

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