Activation of Ovarian Taste Receptors Inhibits Progesterone Production Potentially via NO/cGMP and Apoptotic Signaling

Abstract

Taste receptors are not only expressed in the taste buds, but also in other nongustatory tissues, including the reproductive system. Taste receptors can be activated by various tastants, thereby exerting relatively physiologic functions. The aim of this study was to investigate the effects and potential mechanisms underlying ovarian taste receptor activation on progesterone production using saccharin sodium as the receptor agonist in a pseudopregnant rat model. Taste 1 receptor member 2 (TAS1R2) and taste 2 receptor member 31 (TAS2R31) were demonstrated to be abundantly expressed in the corpora lutea of rats, and intraperitoneal injection of saccharin sodium can activate both of them and initiate their downstream signaling cascades. The activation of these ovarian taste receptors promoted nitric oxide (NO) production via endothelial nitric oxide synthase (eNOS). NO production then increased ovarian cyclic guanosine 3′,5′-monophosphate (cGMP) levels, which, in turn, decreased ovarian cyclic adenosine 3′,5′-monophosphate levels. In addition, the activation of ovarian taste receptors induced apoptosis, possibly through NO and mitogen-activated protein kinase signaling. As a result, the activation of ovarian taste receptors reduced the protein expression of steroidogenesis-related factors, causing the inhibition of ovarian progesterone production. In summary, our data suggest that the activation of ovarian taste receptors inhibits progesterone production in pseudopregnant rats, potentially via NO/cGMP and apoptotic signaling.