Long-Chain Fatty Acids Regulate GnRH Receptor mRNA Expression Level in the Gonadotrope of the Mouse Anterior Pituitary Gland.

Free Fatty acids are not only energy fuels but also signaling molecules. In fact, long-chain fatty acids (LCFAs) have been identified as the ligands for G protein-coupled receptor 120 (GPR120). We have previously observed that GPR120 is richly expressed in the gonadotropes of the mouse anterior pituitary gland and 48hr fasting induces increase in GPR120 mRNA level in the mouse pituitary. Further, in circadian variations, GPR120 mRNA expression levels have shown transient increase at 17:00, GnRH-R mRNA expression levels have decreased between 15:00 and 21:00 and plasma non-esterified fatty acids and triglyceride concentrations have increased between 11:00 and 15:00 in the ad libitum-fed matured male mice. These diurnal variations of GPR120 and GnRH-R in the ad libitum-fed were blunted by time-restricted feeding (feeding time between 06:30-18:30 at light period for 10 days). Based on these results, we hypothesized that the nutrients such as LCFAs act as signaling molecules that regulate gonadal functions at the pituitary level. The aim of present study is to clarify whether LCFAs act as the regulator of gonadotropine releasing hormone receptor (GnRH-R) mRNA in the mouse pituitary. For this purpose, we tried two experiments in this study. First, the effects of high-fat diet for 2 or 30 days on GPR120 and GnRH-R mRNA expression levels were examined in the matured mail mouse pituitaries. Second, the direct effects of palmitate on GPR120 and GnRH-R mRNA expression levels in the mouse pituitary were observed in vivo and in vitro . In the first study, high-fat diet significantly induced increase in GPR120 mRNA expression levels compare to low-fat diet groups in both second and 30 days of high-fat diet and increase in GnRH-R mRNA expression levels in 30 days of high-fat diet. Next, 24 hr treatment of 0.1 mM palmitate directly induced increase in GPR120 mRNA expression levels and decrease in GnRH-R mRNA expression levels in the primary culture cells of the matured male mouse pituitary and gonadotroph cell line, LβT2 in vitro, and GPR120 mRNA expression levels in the mouse pituitary were significantly increased compared with the control in the experiment that administered the palmitate into blood for the short term in vivo. Taken together, these results suggest that LCFAs especially palmitic acid might regulate GnRH receptor mRNA expression levels in the gonadotropes of the mouse anterior pituitary via a specific receptor such as GPR120. Research supported by Grant-in-Aid for Young Scientists (B) 20780202 from the Ministry of Education, Culture, Sports, Science and Technology, Japan and research grant (RK20-028) from Kinki University to R.M.

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