Glutamine and glutamic acid enhance thyroid-stimulating hormone β subunit mRNA expression in the rat pars tuberalis

Abstract

Thyroid-stimulating hormone (TSH)-producing cells of the pars tuberalis (PT) display distinct characteristics that differ from those of the pars distalis (PD). The mRNA expression ofTSHβandαGSUin PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism forTSHβexpression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on laser-captured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of theKA2, which is an ionotropic glutamic acid receptor (iGluR). In addition, the amino acid transporter A2 (ATA2), also known as the glutamine transporter, and glutaminase (GLS), as well asGLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid onTSHβexpression andαGSUexpression in PT slice cultures.l-Glutamine andl-glutamic acid significantly stimulatedTSHβexpression in PT slices after 2- and 4-h treatments, and the effect ofl-glutamic acid was stronger than that ofl-glutamine. In contrast, treatment with glutamine and glutamic acid did not affectαGSUexpression in the PT or the expression ofTSHβorαGSUin the PD. These results strongly suggest that glutamine is taken up by PT cells through ATA2 and that glutamic acid locally converted from glutamine by Gls inducesTSHβexpression via the KA2 in an autocrine and/or paracrine manner in the PT.