EGF-like growth factors as LH mediators in the human corpus luteum

I. Ben-Ami, L. Armon, S. Freimann, D. Strassburger, R. Ron-El, A. Amsterdam

Research output: Contribution to journalArticlepeer-review

46 Scopus citations


BACKGROUND: This study aims to investigate the role of epidermal growth factor-like ligands, amphiregulin (Ar) and epiregulin (Ep), in regulation of apoptosis in luteinized human granulosa cells. METHODS: Luteinized human granulosa cells were obtained from women undergoing IVF treatment. Ar and Ep mRNA levels were measured by real-time RT-PCR. The rate of apoptosis was measured by TUNEL. Progesterone levels were measured using radioimmunoassay. Ar- and Ep-induced activation of signaling cascades and Ar protein levels were detected by western blotting. RESULTS: LH stimulation of luteinized human granulosa cells induced biosynthesis of Ar and Ep mRNA in a time-dependent manner. The blockade of MEK (by U0126) reduced the expression of LH-induced Ar and Ep biosynthesis. Incubation of the cells with Ar and Ep completely abolished the increase in apoptosis rate induced by serum starvation, and concomitantly caused a pronounced increase in progesterone production. Stimulation of the cells with Ar and Ep also activated the ERK and AKT signaling cascades. Finally, we demonstrated that the pro-survival effect of Ar and Ep is partially dependent on their ability to induce progesterone production. CONCLUSIONS: Ar and Ep serve as pro-survival LH mediators in the human corpus luteum.

Original languageEnglish
Pages (from-to)176-184
Number of pages9
JournalHuman Reproduction
Issue number1
StatePublished - Jan 2009
Externally publishedYes

Bibliographical note

Funding Information:
This study was supported by the Women Health Research Center at the Weizmann Institute of Science, Rehovot, Israel.


  • Amphiregulin
  • Apoptosis
  • Corpus luteum
  • Epiregulin
  • Luteinized granulosa cells


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