PGE2 up-regulates EGF-like growth factor biosynthesis in human granulosa cells: new insights into the coordination between PGE2 and LH in ovulation.

Ben-Ami, I; Freimann, S; Armon, L; Dantes, A; Strassburger, D; Friedler, S; Raziel, A; Seger, R; Ron-El, R; Amsterdam, A

Ben-Ami, I; Freimann, S; Armon, L; Dantes, A; Strassburger, D; Friedler, S; Raziel, A; Seger, R; Ron-El, R; Amsterdam, A.

Afiliación

Ben-Ami I; Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot, Israel.

Mol Hum Reprod ; 12(10): 593-9, 2006 Oct.

Article en En | MEDLINE | ID: mdl-16888076

RESUMEN

LH and prostaglandin E(2) (PGE(2)) share many similar effects on the pre-ovulatory follicle. They can induce independently cumulus expansion, the resumption of meiosis and progesterone production. However, cyclooxygenase-2 (COX-2) inhibitors were found to hinder most of the LH-induced effects. Recently, EGF-like growth factors amphiregulin (Ar) and epiregulin (Ep) were found to be produced in response to LH stimulation and to induce cumulus expansion and oocyte maturation. We aimed at evaluating whether PGE(2) induces Ar and Ep syntheses in human granulosa cells and whether the inhibition of PGE(2) production by selective COX-2 inhibitor, nimesulide, affects LH-induced Ar and Ep biosynthesis. Ar and Ep mRNA levels increased following PGE(2) stimulation, in a dose- and time-dependent manner, which resembled those of LH. The blockade of protein kinase A (PKA) (by H89) and mitogen-activated protein kinase (MAPK) (by UO126) reduced the expression of PGE(2)-induced Ar and Ep biosynthesis. Although the stimulation of the cells with LH in the presence of nimesulide did not change the progesterone levels, it resulted in a significant reduction of Ar and Ep biosynthesis. In conclusion, PGE(2) may mimic LH action, at least in part, by the induction of Ar and Ep biosynthesis, which involves cAMP/PKA and MAPK pathways. The negative effect of nimesulide on the ovulatory process may be due to the reduction of Ar and Ep biosynthesis, which implies a possible collaborative role between PGE(2) and LH on their induction.

Asunto(s)

Dinoprostona/metabolismo; Factor de Crecimiento Epidérmico/biosíntesis; Glicoproteínas/biosíntesis; Células de la Granulosa/metabolismo; Péptidos y Proteínas de Señalización Intercelular/biosíntesis; Hormona Luteinizante/metabolismo; Ovulación/metabolismo; Adulto; Anfirregulina; Animales; Células Cultivadas; Proteínas Quinasas Dependientes de AMP Cíclico/metabolismo; Inhibidores de la Ciclooxigenasa 2/farmacología; Dinoprostona/antagonistas & inhibidores; Relación Dosis-Respuesta a Droga; Familia de Proteínas EGF; Factor de Crecimiento Epidérmico/genética; Epirregulina; Femenino; Regulación de la Expresión Génica/efectos de los fármacos; Glicoproteínas/genética; Células de la Granulosa/efectos de los fármacos; Humanos; Péptidos y Proteínas de Señalización Intercelular/genética; Ratones; Ratones Endogámicos C57BL; Proteínas Quinasas Activadas por Mitógenos/metabolismo; Ovulación/efectos de los fármacos; Progesterona/metabolismo; ARN Mensajero/biosíntesis; Transducción de Señal/efectos de los fármacos; Sulfonamidas/farmacología; Factores de Tiempo

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Ovulación / Hormona Luteinizante / Glicoproteínas / Dinoprostona / Péptidos y Proteínas de Señalización Intercelular / Factor de Crecimiento Epidérmico / Células de la Granulosa Límite: Adult / Animals / Female / Humans Idioma: En Revista: Mol Hum Reprod Asunto de la revista: BIOLOGIA MOLECULAR / MEDICINA REPRODUTIVA Año: 2006 Tipo del documento: Article País de afiliación: Israel Pais de publicación: Reino Unido

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