Role of Angiotensin II in the Periovulatory Epidermal Growth Factor-Like Cascade in Bovine Granulosa Cells In Vitro1

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.

Role of angiotensin in ovarian follicular development and ovulation in mammals: a review of recent advances

“…At the end of the follicular phase, a complex series of events culminates in ovulation, with the release of a competent egg and the initiation of luteal development. Ang II has been demonstrated to be essential in the ovulatory process (Ferreira et al 2007) and seems to be an important mediator of LH action in the early increase in ADAM activity that induces the cascade of events leading to ovulation (Portela et al 2011). However, the physiological function of Ang II in the ovary is not yet well established and the wide species variation makes its understanding even more challenging (Bottari et al 1993, Nielsen et al 1995, Yoshimura 1997, Mow et al 1999.…”

Activation of the renin-angiotensin-aldosterone system in mares around ovulation

“…expression of renin (REN), angiotensin (ANG), and aldosterone (ALD) in uterus, and in granulosa and thecal cells of ovarian follicles (Portela et al 2011). As a result, there are increased circulating concentrations of these hormones in women (Chapman et al 1997;Chidambaram et al 2002;Szmuilowicz et al 2006).…”

Steroidogenic enzymes mRNA expression profile and steroids production in bovine theca cells cultured in vitro and stimulated with angiotensin II

“…These differences are likely due to a specie-specific factors since the RAS system is not uniform in mammals (GONÇALVES et al, 2012). In bovine, there was no effect of Ang II alone or in association with LH on androstenedione or testosterone synthesis in theca cells, neither on progesterone production induced by LH in granulosa cells (PORTELA et al, 2011). Additionally, it was observed a significant decrease in mRNA abundance for the enzyme CYP19A1 in granulosa cells of dominant follicles after intrafollicular injection of saralasin (FERREIRA et al, 2011a).…”

“…Ang II participates in the synthesis of estrogen through CYP19A1 during follicular deviation (FERREIRA et al, 2011b). However, it did not stimulate progesterone production and LH-induced STAR expression (PORTELA et al, 2011). In theca cells, there was no difference in mRNA expression for CYP17A1, HSD3B2 and STAR between dominant follicles treated with saralasin or vehicle during follicular deviation (FERREIRA et al, 2011a).…”