PMID- 21849708 OWN - NLM STAT- MEDLINE DCOM- 20120412 LR - 20161125 IS - 1529-7268 (Electronic) IS - 0006-3363 (Linking) VI - 85 IP - 6 DP - 2011 Dec TI - Role of angiotensin II in the periovulatory epidermal growth factor-like cascade in bovine granulosa cells in vitro. PG - 1167-74 LID - 10.1095/biolreprod.111.094193 [doi] AB - 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. FAU - Portela, Valerio M AU - Portela VM AD - Centre de Recherche en Reproduction Animale, Universite de Montreal, St-Hyacinthe, Quebec, Canada. FAU - Zamberlam, Gustavo AU - Zamberlam G FAU - Goncalves, Paulo B D AU - Goncalves PB FAU - de Oliveira, Joao F C AU - de Oliveira JF FAU - Price, Christopher A AU - Price CA LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110817 PL - United States TA - Biol Reprod JT - Biology of reproduction JID - 0207224 RN - 0 (Amphiregulin) RN - 0 (Epiregulin) RN - 0 (Glycoproteins) RN - 0 (Intercellular Signaling Peptides and Proteins) RN - 11128-99-7 (Angiotensin II) RN - 62229-50-9 (Epidermal Growth Factor) RN - 9002-67-9 (Luteinizing Hormone) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 3.4.24.- (ADAM Proteins) RN - EC 3.4.24.86 (ADAM17 Protein) SB - IM MH - ADAM Proteins/metabolism MH - ADAM17 Protein MH - Amphiregulin MH - Angiotensin II/*physiology MH - Animals MH - Cattle MH - *Cell Culture Techniques MH - Cells, Cultured MH - Cyclooxygenase 2/metabolism MH - Epidermal Growth Factor/metabolism MH - Epiregulin MH - Female MH - Glycoproteins/metabolism MH - Granulosa Cells/*metabolism MH - Intercellular Signaling Peptides and Proteins/metabolism MH - Luteinizing Hormone/*physiology MH - *Ovulation EDAT- 2011/08/19 06:00 MHDA- 2012/04/13 06:00 CRDT- 2011/08/19 06:00 PHST- 2011/08/19 06:00 [entrez] PHST- 2011/08/19 06:00 [pubmed] PHST- 2012/04/13 06:00 [medline] AID - biolreprod.111.094193 [pii] AID - 10.1095/biolreprod.111.094193 [doi] PST - ppublish SO - Biol Reprod. 2011 Dec;85(6):1167-74. doi: 10.1095/biolreprod.111.094193. Epub 2011 Aug 17.