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

Autor: A. Amsterdam, Arieh Raziel, S. Freimann, Devorah Strassburger, Leah Armon, Shevach Friedler, R. Seger, Ada Dantes, Ido Ben-Ami, Raphael Ron-El
Rok vydání: 2006
Předmět:
Adult
Ovulation
MAPK/ERK pathway
EGF Family of Proteins
Embryology
medicine.medical_specialty
Time Factors
Granulosa cell
Stimulation
Biology
Amphiregulin
Dinoprostone
Epiregulin
Mice
Internal medicine
Genetics
medicine
Animals
Humans
RNA
Messenger
Prostaglandin E2
Ovarian follicle
Protein kinase A
Molecular Biology
Cells
Cultured
Progesterone
Glycoproteins
Sulfonamides
Granulosa Cells
Cyclooxygenase 2 Inhibitors
Dose-Response Relationship
Drug
Epidermal Growth Factor
Obstetrics and Gynecology
Cell Biology
Luteinizing Hormone
Cyclic AMP-Dependent Protein Kinases
Mice
Inbred C57BL
Endocrinology
medicine.anatomical_structure
Gene Expression Regulation
Reproductive Medicine
Intercellular Signaling Peptides and Proteins
Female
Mitogen-Activated Protein Kinases
Luteinizing hormone
Signal Transduction
Developmental Biology
medicine.drug
Zdroj: MHR: Basic science of reproductive medicine. 12:593-599
ISSN: 1460-2407
1360-9947
Popis: 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.
Databáze: OpenAIRE
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