A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics

Michael W OʼReilly, Connar Westgate, Catherine Hornby, Hannah Botfield, Angela Taylor, Keira Markey, James Mitchell, William Scotton, Susan Mollan, Andreas Yiangou, Carl Jenkinson, Lorna Gilligan, Mark Sherlock, James Gibney, Jeremy W Tomlinson, Gareth Lavery, David Hodson, Wiebke Arlt, Alexandra Sinclair

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)
147 Downloads (Pure)

Abstract

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.

Original languageEnglish
Article numbere125348
JournalJCI Insight
Volume4
Issue number6
Early online date12 Feb 2019
DOIs
Publication statusPublished - 21 Mar 2019

Keywords

  • Idiopathic intracranial hypertension
  • pathogenesis
  • androgen excess

Fingerprint

Dive into the research topics of 'A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics'. Together they form a unique fingerprint.

Cite this