The ERK signaling cascade inhibits gonadotropin-stimulated steroidogenesis

R Seger1, T Hanoch, R Rosenberg

  • 1Departments of Biological Regulation and Molecular Cell Biology, the Weizmann Institute of Science, Rehovot 71600, Israel. rony.seger@weizmann.ac.il

Insights

Luteinizing hormone (LH) and follicle-stimulating hormone (FSH) stimulate progesterone production in granulosa cells via PKA signaling. However, the ERK pathway down-regulates this process by reducing steroidogenic acute regulatory protein (StAR) expression.

Area of Science:

  • Reproductive Endocrinology
  • Cell Signaling
  • Molecular Biology

Background:

  • Granulosa cell response to LH and FSH is primarily mediated by cAMP/protein kinase A (PKA) signaling.
  • Extracellular signal-regulated kinase (ERK) signaling is also activated by these gonadotropins.

Purpose of the Study:

  • To investigate the role of the ERK signaling cascade in LH- and FSH-induced steroidogenesis in granulosa-derived cell lines.
  • To elucidate the regulatory mechanisms of gonadotropin-stimulated progesterone production.

Main Methods:

  • Utilized two granulosa-derived cell lines (rLHR-4 and rFSHR-17).
  • Stimulated cells with appropriate gonadotropins (LH or FSH).
  • Assessed ERK activation, progesterone production, and steroidogenic acute regulatory protein (StAR) expression.
  • Inhibited ERK activity to observe effects on steroidogenesis.

Main Results:

  • Gonadotropin stimulation induced both ERK activation and progesterone production downstream of PKA.
  • Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production.
  • Enhanced progesterone production correlated with increased StAR expression upon ERK inhibition.

Conclusions:

  • Gonadotropin-stimulated progesterone formation involves PKA and StAR, with ERK acting as a down-regulator by attenuating StAR expression.
  • Activation of PKA signaling by gonadotropins not only induces steroidogenesis but also triggers ERK-mediated down-regulation.
  • ERK activation by gonadotropins is a key mechanism modulating gonadotropin-induced steroidogenesis.

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