Details

Autor(en) / Beteiligte

• Seger, R
• Hanoch, T
• Rosenberg, R
• Dantes, A
• Merz, W E
• Strauss, 3rd, J F
• Amsterdam, A

Titel

The ERK Signaling Cascade Inhibits Gonadotropin-stimulated Steroidogenesis

Ist Teil von

• The Journal of biological chemistry, 2001-04, Vol.276 (17), p.13957-13964

Ort / Verlag

United States: American Society for Biochemistry and Molecular Biology

Erscheinungsjahr

2001

Link zum Volltext

Quelle

Electronic Journals Library

Beschreibungen/Notizen

• The response of granulosa cells to luteinizing hormone (LH) and follicle-stimulating hormone (FSH) is mediated mainly by cAMP/protein kinase A (PKA) signaling. Notably, the activity of the extracellular signal-regulated kinase (ERK) signaling cascade is elevated in response to these stimuli as well. We studied the involvement of the ERK cascade in LH- and FSH-induced steroidogenesis in two granulosa-derived cell lines, rLHR-4 and rFSHR-17, respectively. We found that stimulation of these cells with the appropriate gonadotropin induced ERK activation as well as progesterone production downstream of PKA. Inhibition of ERK activity enhanced gonadotropin-stimulated progesterone production, which was correlated with increased expression of the steroidogenic acute regulatory protein (StAR), a key regulator of progesterone synthesis. Therefore, it is likely that gonadotropin-stimulated progesterone formation is regulated by a pathway that includes PKA and StAR, and this process is down-regulated by ERK, due to attenuation of StAR expression. Our results suggest that activation of PKA signaling by gonadotropins not only induces steroidogenesis but also activates down-regulation machinery involving the ERK cascade. The activation of ERK by gonadotropins as well as by other agents may be a key mechanism for the modulation of gonadotropin-induced steroidogenesis.