Control of the adrenocortical cell cycle: interaction between FGF2 and ACTH

H A Armelin1, C F Lotfi

  • 1Departamento de Bioquímica, Universidade de São Paulo, Brasil.

Insights

Fibroblast Growth Factor 2 (FGF2) strongly stimulates Y-1 cell growth by activating ERK-MAPK and c-Fos. Adrenocorticotropic Hormone (ACTH) blocks this FGF2 effect, revealing insights into adrenocortical cell regulation.

Area of Science:

  • Endocrinology
  • Cell Biology
  • Molecular Biology

Background:

  • Fibroblast Growth Factor 2 (FGF2) is a potent mitogen for mouse Y-1 adrenocortical tumor cells.
  • This mitogenic response involves the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) cascade and c-Fos protein induction.
  • Adrenocorticotropic Hormone (ACTH) is a weak mitogen but can modulate cellular responses.

Purpose of the Study:

  • To investigate the interaction between FGF2 and ACTH in regulating Y-1 cell proliferation.
  • To elucidate the molecular mechanisms underlying ACTH's modulation of FGF2-induced mitogenesis.
  • To uncover signaling pathways involved in adrenocortical cell growth regulation.

Main Methods:

  • Utilized mouse Y-1 adrenocortical tumor cell line.
  • Stimulated cells with FGF2 and ACTH, individually and in combination.
  • Monitored ERK-MAPK cascade activation and c-Fos protein induction.
  • Assessed cell proliferation and cell cycle progression.

Main Results:

  • FGF2 induced rapid and transient ERK-MAPK activation and c-Fos expression in Y-1 cells.
  • ACTH, a weak mitogen, inhibited the mitogenic effects of FGF2.
  • ACTH maintained maximal ERK-MAPK activation and c-Fos induction despite blocking FGF2's mitogenic effect.
  • ACTH interfered with FGF2's mitogenic action during early and mid-G1 phase.

Conclusions:

  • ACTH antagonizes FGF2-driven proliferation in Y-1 cells by modulating specific cell cycle phases.
  • The interplay between FGF2 and ACTH signaling provides insights into the complex regulation of adrenocortical cell growth.
  • Understanding these interactions is crucial for comprehending normal and pathological adrenocortical function.

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