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  • Title: EGF-like growth factors as LH mediators in the human corpus luteum.
    Author: Ben-Ami I, Armon L, Freimann S, Strassburger D, Ron-El R, Amsterdam A.
    Journal: Hum Reprod; 2009 Jan; 24(1):176-84. PubMed ID: 18835871.
    Abstract:
    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.
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