Background:

Androsterone is a metabolic product of testosterone and can activate Farnesoid X Receptor (FXR).

Androsterone activates both the mFXR-LBD and the hFXR-LBD, with Androsterone activating the mFXR-LBD more strongly than the hFXR-LBD. Furthermore, cotransfection studies with gal4-hFXR-LBD and SRC-1/VP16 expression plasmids demonstrate that Androsterone potentiates the interaction of SRC-1 with the hFXR-LBD. Several amino acid changes including H294S, S332V, R351H, and Y361F significantly reduce Androsterone activation[1]. Androsterone (5α, 3α-A) (10 to 100 μM) also inhibits epileptiform discharges in a concentration-dependent fashion in the in vitro slice model[2].

Androsterone treatment results in a significant induction of small heterodimer partner (SHP), suggesting Androsterone may activate endogenous FXR[1]. Intraperitoneal injection of Androsterone (5α, 3α-A) protects mice in a dose-dependent fashion from seizures in the following models (ED50, dose in mg/kg protecting 50% of animals): 6 Hz electrical stimulation (29.1), pentylenetetrazol (43.5), pilocarpine (105), 4-AP (215), and maximal electroshock (224)[2].

[1]. Wang S, et al. The nuclear hormone receptor farnesoid X receptor (FXR) is activated by androsterone. Endocrinology. 2006 Sep;147(9):4025-33. [2]. Kaminski RM, et al. Anticonvulsant activity of androsterone and etiocholanolone. Epilepsia. 2005 Jun;46(6):819-27.