Involvement of GPR4 in increased growth hormone and prolactin expressions by extracellular acidification in MtT/S cells

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  • MUSHA Shiori
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
  • YOSHIDA Saishu
    Department of Biochemistry, Jikei University School of Medicine, Tokyo 105-8461, Japan
  • MURAKAMI Syo
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
  • KOJIMA Ryotaro
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
  • DEAI Masahito
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
  • SASO Naoshi
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan
  • MOGI Chihiro
    Laboratory of Integrated Signaling Systems, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
  • SATO Koichi
    Laboratory of Medical Neuroscience, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512, Japan
  • OKAJIMA Fumikazu
    Laboratory of Pathophysiology, Faculty of Pharmacy, Aomori University, Aomori 030-0943, Japan
  • TOMURA Hideaki
    Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571, Japan Institute of Endocrinology, Meiji University, Kawasaki 214-8571, Japan

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  • Involvement of GPR4 in increased <i>growth hormone</i> and <i>prolactin</i> expressions by extracellular acidification in MtT/S cells

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<p> Hormone-secreting pituitary adenomas show unregulated hormonal hypersecretion and cause hyperpituitarism. However, the mechanism of the unregulated hormone production and secretion has not yet been fully elucidated. Solid tumors show reduced extracellular pH, partly due to lactate secretion from anaerobic glycolysis. It is known that extracellular acidification affects hormone secretion. However, whether and how the extracellular acidification influences the unregulated hormone production and secretion remain unknown. In the present study, we found that GPR4, a proton-sensing G protein-coupled receptor, was highly expressed in MtT/S cells, a growth hormone-producing and prolactin-producing pituitary tumor cell line. When we reduced the extracellular pH, growth hormone and prolactin mRNA expressions increased in the cells. Both increased expressions were partially suppressed by a GPR4 antagonist. We also found that extracellular acidification enhanced growth hormone-releasing factor-induced growth hormone secretion from MtT/S cells. These results suggest that GPR4 may play a role in hypersecretion of the hormone from hormone-producing pituitary tumors. A GPR4 antagonist will be a useful tool for preventing the hypersecretion.</p>

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