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Region Hovedstaden - en del af Københavns Universitetshospital
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A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics

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  • Michael W O'Reilly
  • Connar Sj Westgate
  • Catherine Hornby
  • Hannah Botfield
  • Angela E Taylor
  • Keira Markey
  • James L Mitchell
  • William J Scotton
  • Susan P Mollan
  • Andreas Yiangou
  • Carl Jenkinson
  • Lorna C Gilligan
  • Mark Sherlock
  • James Gibney
  • Jeremy W Tomlinson
  • Gareth G Lavery
  • David J Hodson
  • Wiebke Arlt
  • Alexandra J Sinclair
Vis graf over relationer

Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology, characterized by elevated intracranial pressure frequently manifesting with chronic headaches and visual loss. Similar to polycystic ovary syndrome (PCOS), IIH predominantly affects obese women of reproductive age. In this study, we comprehensively examined the systemic and cerebrospinal fluid (CSF) androgen metabolome in women with IIH in comparison with sex-, BMI-, and age-matched control groups with either simple obesity or PCOS (i.e., obesity and androgen excess). Women with IIH showed a pattern of androgen excess distinct to that observed in PCOS and simple obesity, with increased serum testosterone and increased CSF testosterone and androstenedione. Human choroid plexus expressed the androgen receptor, alongside the androgen-activating enzyme aldoketoreductase type 1C3. We show that in a rat choroid plexus cell line, testosterone significantly enhanced the activity of Na+/K+-ATPase, a surrogate of CSF secretion. We demonstrate that IIH patients have a unique signature of androgen excess and provide evidence that androgens can modulate CSF secretion via the choroid plexus. These findings implicate androgen excess as a potential causal driver and therapeutic target in IIH.

OriginalsprogEngelsk
TidsskriftJCI Insight
Vol/bind4
Udgave nummer6
Sider (fra-til)e125348
ISSN2379-3708
DOI
StatusUdgivet - 2019
Eksternt udgivetJa

ID: 58957867