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

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

Research output: Contribution to journalArticle

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)357-365
Number of pages9
JournalJournal of Neuroendocrinology
Volume24
Issue number2
DOIs
Publication statusPublished - 2012 Feb

Fingerprint

Extracellular Signal-Regulated MAP Kinases
Epidermal Growth Factor
Growth Hormone
Tretinoin
Mitogen-Activated Protein Kinases
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Mitogen-Activated Protein Kinase Kinases
Phosphorylation
Cell Line
Clone Cells
Cell Proliferation
Messenger RNA

Keywords

  • Epidermal growth factor
  • Growth hormone
  • Mitogen-activated protein kinase
  • Proliferation

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism
  • Endocrine and Autonomic Systems
  • Cellular and Molecular Neuroscience

Cite this

Epidermal Growth Factor-Activated Extracellular Signal-Regulated Kinase Suppresses Growth Hormone Expression and Stimulates Proliferation in MtT/E Cells. / Nogami, H.; Soya, H.; Hiraoka, Yoshiki; Aiso, S.; Hisano, S.

In: Journal of Neuroendocrinology, Vol. 24, No. 2, 02.2012, p. 357-365.

Research output: Contribution to journalArticle

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abstract = "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.",
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AB - 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.

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