Epidermal Growth Factor-Activated Extracellular Signal-Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/E Cells

H. Nogami, H. Soya, Y. Hiraoka, S. Aiso, S. Hisano

研究成果: Article査読

5 被引用数 (Scopus)

抄録

The mechanism for the inhibition of growth hormone (GH) expression by the epidermal growth factor (EGF) was examined in two clonal cell lines, MtT/E and MtT/S. The former has a negligible basal level of GH, whereas the latter has a high basal GH. The treatment of MtT/E cells with retinoic acid resulted in a significant increase in GH mRNA and subsequently GH. This stimulatory response to retinoic acid was strongly suppressed by EGF. This suppression was associated with an increase in the phosphorylation of extracellular signal-regulated kinase 1 and 2 (Erk1/2). The MEK [mitogen-activated protein kinase (MAPK) kinases that activate ERK1 and ERK2] inhibitor, PD98059, clearly inhibited the phosphorylation of Erk1/2 and restored the stimulatory effects of retinoic acid. These results suggest that the inhibitory effects of EGF on GH expression are mediated by MAPK activation in these cells. By contrast to the GH-producing clones examined previously, EGF showed a marked stimulation of proliferation of the MtT/E cells through a mechanism dependent on MAPK activation. On the other hand, the inhibitory effect of EGF on GH expression was less pronounced and the stimulation of cellular proliferation was not seen in MtT/S cells, even though it induced Erk-phosphorylation similar to that seen in MtT/E. The distinct difference in the response to EGF between these two GH cell lines appears to be attributed to differences in the function of MAPK cascade in each cell line. This may reflect the developmental stage of the cells from which MtT/E and MtT/S are derived.

本文言語English
ページ(範囲)357-365
ページ数9
ジャーナルJournal of Neuroendocrinology
24
2
DOI
出版ステータスPublished - 2012 2

ASJC Scopus subject areas

  • 内分泌学、糖尿病および代謝内科学
  • 内分泌学
  • 内分泌系および自律システム
  • 細胞および分子神経科学

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