Endocrine Abstracts (2007) 13 P237

A putative role for 11β-Hydroxysteroid dehydrogenase 1 in the regulation of cerebrospinal fluid dynamics

Alexandra Sinclair1, Claire Onyimba1, Pamela Khosla1, Jeremy Tomlinson2, Michael Burdon1, Philip Murray1, Paul Stewart2, Elizabeth Walker2 & Saaeha Rauz1

1Academic Unit of Ophthalmology, Division of Immunity and Infection, University of Birmingham, Birmingham, United Kingdom; 2Department of Endocrinology, Division of Medical Sciences, University of Birmingham, Birmingham, United Kingdom.

The pre-receptor regulation of glucocorticoids is mediated by 11β-hydroxysteroid dehydrogenases (11β-HSD). The type 1 isoform is primarily responsible for the generation of active cortisol in tissues such as liver and adipose, whereas 11β-HSD2 regulates sodium and ion transport. Recently, we have shown the presence of functional 11β-HSD1 in the ciliary body of the eye where it is important in control of sodium transport, aqueous humour production and intraocular pressure. We propose that a similar mechanism may exist in the embryologically-related epithelial cells of the choroid plexus (CP), which are responsible for sodium regulation and hence cerebrospinal fluid (CSF) production in the brain. CSF circulates from the CP through the intra-cerebral ventricular system, draining predominantly through the arachnoid granulation tissue (AGT). The balance between production and drainage of CSF gives rise in part to intracranial pressure. The aim of this study was to characterise CP and AGT as steroid target tissues.

Immunolocalisation studies on 5 μm sections of human tissue, identified 11β-HSD1 in the CP epithelium. These findings were endorsed by activity studies in whole tissue CP explants which confirmed by-directional activity, all though this was predominantly oxo-reductase generating active cortisol (cortisone to cortisol 24±11 pmol/g/h; cortisol to cortisone 3±3 pmol/g/h).RT-PCR analysis of CP tissue and a primary untransformed human choroid plexus epithelial cell line defined mRNA expression for 11β-HSD1, hexose-6-phosphate dehydrogenase, glucocorticoid receptor, mineralocorticoid receptor, androgen receptor and oestrogen receptor β. An identical pattern of mRNA expression was found in the AGT although whole tissue explants failed to convert cortisone to cortisol.

We have identified a novel cortisol generating system in the CP which may represent an underlying mechanism controlling CSF dynamics. 11β-HSD1 may therefore be important in the regulation of intracranial pressure.

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