Pituitary tumors (PTs) can cause significant mortality and morbidity due to limited therapeutic options. L-type amino acid transporters (LATs), in particular, the LAT1 isoform, is expressed in a variety of tumor cells. Pharmacological inhibition or genetic ablation of LAT1 can suppress leucine transport into cancer cells, resulting in suppression of cancer cell growth. However, roles of LAT1 in PTs have not been elucidated. Therefore, we assessed LAT1 expression in PTs and evaluated a LAT1-specific inhibitor, JPH203, on rat somatomammotroph tumor cells, GH4 cells. GH4 cells dominantly express LAT1 mRNA rather than other LAT isoforms, whereas LAT2 transcripts were most abundant in normal rat pituitary tissues. JPH203 inhibited leucine uptake and cell growth in GH4 cells in a concentration-dependent manner, and appeared to be independent of the mechanistic target, the rapamycin pathway. Although JPH203 did not induce apoptosis, it suppressed growth hormone production in GH4 cells. Also, genetic downregulation of LAT1 showed similar effects on cell growth and hormone production. These results indicated that restriction of LAT1 substrates by JPH203 modulated both cell growth and hormone production. In conclusion, LAT1 may be a new therapeutic target for PTs because its inhibition leads to suppression of cell growth as well as hormone production. JPH203 may represent a promising drug for clinical use in patients with PTs, with the potential of hormonal control and tumor suppression.

垂体肿瘤（PTs）由于治疗选择有限，可能导致明显的死亡率和发病率。L型氨基酸转运蛋白（LAT），特别是LAT1同工型，在多种肿瘤细胞中表达。LAT1的药理抑制或遗传消融可以抑制亮氨酸转运到癌细胞中，从而抑制癌细胞的生长。但是，尚未阐明LAT1在PT中的作用。因此，我们评估了大鼠PT4中LAT1的表达，并评估了LAT1特异性抑制剂JPH203。GH4细胞主要表达LAT1 mRNA，而不是其他LAT亚型，而正常大鼠垂体组织中LAT2转录本最为丰富。JPH203以浓度依赖性方式抑制GH4细胞中的亮氨酸摄取和细胞生长，并且似乎独立于机械目标雷帕霉素途径。尽管JPH203不诱导细胞凋亡，但它抑制了GH4细胞中的生长激素产生。同样，LAT1的基因下调对细胞生长和激素产生显示出相似的影响。这些结果表明，JPH203对LAT1底物的限制可调节细胞生长和激素产生。总之，LAT1可能是PT的新治疗靶标，因为它的抑制导致细胞生长以及激素产生的抑制。JPH203可能代表有前景的药物，在PT患者中临床应用，具有激素控制和抑制肿瘤的潜力。LAT1的基因下调显示出对细胞生长和激素产生的类似作用。这些结果表明，JPH203对LAT1底物的限制可调节细胞生长和激素产生。总之，LAT1可能是PT的新治疗靶标，因为它的抑制导致细胞生长以及激素产生的抑制。JPH203可能代表有前景的药物，在PT患者中临床应用，具有激素控制和抑制肿瘤的潜力。LAT1的基因下调显示出对细胞生长和激素产生的类似作用。这些结果表明，JPH203对LAT1底物的限制可调节细胞生长和激素产生。总之，LAT1可能是PT的新治疗靶标，因为它的抑制导致细胞生长以及激素产生的抑制。JPH203可能代表有前景的药物，在PT患者中临床应用，具有激素控制和抑制肿瘤的潜力。