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

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 of TSHb and aGSU in PT has a circadian rhythm and is inhibited by melatonin via melatonin receptor type 1; however, the detailed regulatory mechanism for TSHb expression in the PT remains unclear. To identify the factors that affect PT, a microarray analysis was performed on lasercaptured PT tissue to screen for genes coding for receptors that are abundantly expressed in the PT. In the PT, we found high expression of the KA2, 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 as GLS2, were highly expressed in the PT compared to the PD. We examined the effects of glutamine and glutamic acid on TSHb expression and aGSU expression in PT slice cultures. L-Glutamine and L-glutamic acid significantly stimulated TSHb expression in PT slices after 2- and 4-h treatments, and the effect of L-glutamic acid was stronger than that of L-glutamine. In contrast, treatment with glutamine and glutamic acid did not affect aGSU expression in the PT or the expression of TSHb or aGSU in 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 induces TSHb expression via the KA2 in an autocrine and/or paracrine manner in the PT. [ABSTRACT FROM AUTHOR]