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17 August 2011 Role of Angiotensin II in the Periovulatory Epidermal Growth Factor-Like Cascade in Bovine Granulosa Cells In Vitro
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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.

Valério M. Portela, Gustavo Zamberlam, Paulo B.D. Gonçalves, João F.C. de Oliveira, and Christopher A. Price "Role of Angiotensin II in the Periovulatory Epidermal Growth Factor-Like Cascade in Bovine Granulosa Cells In Vitro," Biology of Reproduction 85(6), 1167-1174, (17 August 2011). https://doi.org/10.1095/biolreprod.111.094193
Received: 28 June 2011; Accepted: 1 July 2011; Published: 17 August 2011
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