Bitter taste signaling mediated by Tas2r144 is down-regulated by 17β-estradiol and progesterone in the rat choroid plexus

Abstract

The blood-cerebrospinal fluid barrier is constituted by choroid plexus epithelial cells (CPEC) that regulate molecular trafficking between the blood and the cerebrospinal fluid. We hypothesize that taste receptors expressed in CPEC monitor the composition of these body fluids in a sex hormone dependent way. Thus, we compared the expression of taste related genes in the choroid plexus of sham and ovariectomized female rats, and then studied the effect of 17β-estradiol and progesterone in their expression and function. We found that the bitter receptors Tas2r109, Tas2r144, and the taste-related genes Plcb2 and Trpm5 were down-regulated by ovarian hormones in vivo and ex vivo with functional implications. Knocking-down Tas2r144 with a specific siRNA in a CPEC line (Z310) effectively reduced the Ca2+ response to the bitter compound denatonium benzoate, in a similar manner to female sex hormones alone, suggesting that female sex hormones downregulated the responses of CPEC to chemical stimuli by reducing Tas2r144.