title: Role of angiotensin II in the periovulatory epidermal growth factor-like cascade in bovine granulosa cells in vitro.
abstract: Angiotensin II (AGT-2) induces follicular prostaglandin release in a number of species and ovulation in rabbits. Conversely, AGT-2 antagonists block ovulation in cattle. To determine the mechanism of action of AGT-2, we used a bovine granulosa cell model in which luteinizing hormone (LH) increased the expression of genes essential for ovulation in a time- and dose-dependent manner. The addition of AGT-2 to LH-stimulated cells significantly increased abundance of prostaglandin-endoperoxide synthase 2 (PTGS2) mRNA and protein, whereas AGT-2 alone had no effect. Upstream of PTGS2, AGT-2 increased abundance of mRNA encoding the epidermal growth factor-like ligands amphiregulin (AREG) and epiregulin (EREG) at 6 h posttreatment and abundance of a disintegrin and metalloprotease 17 (ADAM17), a sheddase, within 3 h of treatment. Inhibiting sheddase activity abolished the stimulatory effect of AGT-2 on AREG, EREG, and PTGS2 mRNA. The addition of selective AGT-2 antagonists to cells stimulated with LH plus AGT-2 demonstrated that AGT-2 did not act through the type 1 receptor and did not increase mitogen-activated protein kinase 3/1 phosphorylation. Combined with previous data from studies in vitro, we conclude that AGT-2 is an essential cofactor for LH in the early increase of ADAM expression/activity that induces the cascade of events leading to ovulation.
authors.affiliation: Centre de Recherche en Reproduction Animale, Université de Montréal, St-Hyacinthe, Quebec, Canada.
authors.forename: Valério M
authors.initials: VM
authors.lastname: Portela
authors.forename: Gustavo
authors.initials: G
authors.lastname: Zamberlam
authors.forename: Paulo B D
authors.initials: PB
authors.lastname: Gonçalves
authors.forename: João F C
authors.initials: JF
authors.lastname: de Oliveira
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Price
mesh_terms: D051722:ADAM Proteins / Q000378:metabolism; D000072198:ADAM17 Protein; D066258:Amphiregulin; D000804:Angiotensin II / Q000502:physiology*; D000818:Animals; D002417:Cattle; D018929:Cell Culture Techniques; D002478:Cells, Cultured; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D066260:Epiregulin; D005260:Female; D006023:Glycoproteins / Q000378:metabolism; D006107:Granulosa Cells / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D007986:Luteinizing Hormone / Q000502:physiology*; D010060:Ovulation
chemical_list: D066258:Amphiregulin; D066260:Epiregulin; D006023:Glycoproteins; D036341:Intercellular Signaling Peptides and Proteins; D000804:Angiotensin II; D004815:Epidermal Growth Factor; D007986:Luteinizing Hormone; D051546:Cyclooxygenase 2; D051722:ADAM Proteins; D000072198:ADAM17 Protein