Sweet Taste Receptor T1R3 Expressed in Leydig Cells Is Closely Related to Homeostasis of the Steroid Hormone Metabolism Profile

Taste receptor type 1 subunit 3 (T1R3) is initially expressedinmammal tongue for recognition and response of sweet/umami tastantsand is critical to nutrient absorption, even endocrine. In this study,down-regulation of related steroidogenic enzymes such as StAR, 3 beta-HSD,CYP17A1, and 17 beta-HSD with the decrease of T1R3 expression wasfound in Leydig cells treated by a T1R3 inhibitor (lactisole). Theabundances of progesterone, 17a-hydroxyprogesterone, androstenedione,testosterone, and deoxycorticosterone were down-regulated by 2.3,3.5, 1.4, 1.6, and 2.2 times, respectively, after T1R3 inhibition.In addition, opposite results were found in saccharin sodium treatment.T1R3 activation contributed to intracellular cyclic adenosine monophosphate(cAMP) accumulation (14.41 +/- 0.58 vs 20.21 +/- 0.65) and increasedtestosterone (20.31 +/- 3.49 vs 50.01 +/- 7.44) and steroidogenicmetabolite levels. Coadministration of human chorionic gonadotropinand saccharin sodium resulted in elevating the testosterone and cAMPlevels and enhancing the expression levels of steroidogenic-relatedfactors. Similarly, intratesticular injection of lactisole and saccharinsodium further confirmed that T1R3 inhibition/activation affectedthe expression of related steroidogenic enzymes and the testosteronelevels in mice. The above findings suggest that T1R3 plays a rolein testicular steroidogenesis.