Diazepam binding inhibitor (DBI) reduces testosterone and estradiol levels in vivo

Abstract

Diazepam binding inhibitor (DBI) is a putative endogenous ligand capable of binding to the central type benzodiazepine (BZD) receptor located on the GABA A receptor and the peripheral type BZD receptor on the mitochondrial outer membrane. We examined the effects of an intracerebroventricular injection of DBI on the serum levels of the gonadal hormones, testosterone and estradiol, respectively, in male and female mice. DBI (0.3–10 nmol/mouse, i.c.v.) significantly reduced the levels of both gonadal hormones in a dose-dependent manner. The decrease in the gonadal hormone levels became evident at 1 hr and lasted for at least 4 hrs after the DBI injection. The effects of DBI (3 nmol/mouse, i.c.v.) in male and female mice were completely attenuated by the coadministration of flumazenil (66 nmol/mouse), a selective antagonist for the central type BZD receptor. These results suggest that DBI acts as an endogenous modulator to regulate the levels of gonadal hormones in vivo, and that the DBI-induced decrease in gonadal hormone levels is mediated by down regulation of the GABAergic system, implicated in gonadotropin-releasing systems and/or the hypothalamic-pituitary-gonadal axis.