TY - JOUR

T1 - A unique androgen excess signature in idiopathic intracranial hypertension is linked to cerebrospinal fluid dynamics

AU - O'Reilly, Michael W

AU - Westgate, Connar Sj

AU - Hornby, Catherine

AU - Botfield, Hannah

AU - Taylor, Angela E

AU - Markey, Keira

AU - Mitchell, James L

AU - Scotton, William J

AU - Mollan, Susan P

AU - Yiangou, Andreas

AU - Jenkinson, Carl

AU - Gilligan, Lorna C

AU - Sherlock, Mark

AU - Gibney, James

AU - Tomlinson, Jeremy W

AU - Lavery, Gareth G

AU - Hodson, David J

AU - Arlt, Wiebke

AU - Sinclair, Alexandra J

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

U2 - 10.1172/jci.insight.125348

DO - 10.1172/jci.insight.125348

M3 - Journal article

VL - 4

SP - e125348

JO - JCI Insight

JF - JCI Insight

SN - 2379-3708

IS - 6

ER -