Angiotensin II Signaling Promotes Follicle Growth and Dominance in Cattle

Abstract

It is generally understood that angiotensin II (AngII) promotes follicle atresia in rats, although recent data suggested that this may not be true in cattle. In this study, we aimed to determine in vivo whether AngII alters follicle development in cattle, using intrafollicular injection of AngII or antagonist into the growing dominant follicle or the second largest subordinate follicle. Injection of saralasin, an AngII antagonist, into the growing dominant follicle inhibited follicular growth, and this inhibitory effect was overcome by systemic FSH supplementation. Injection of AngII into the dominant follicle did not affect follicular growth, whereas injection of AngII into the second largest follicle prevented the expected atresia of this subordinate follicle, and the treated follicle grew at the same rate as the dominant follicle for the next 24 h. Inhibition of AngII action in the dominant follicle decreased estradiol concentrations in follicular fluid and the abundance of mRNA encoding aromatase, 3β-hydroxysteroid dehydrogenase, LH receptor, and cyclinD2 in granulosa cells, with minimal effects on theca cells. The effect of AngII on aromatase mRNA levels was confirmed using an in vitro granulosa cell culture system. In conclusion, these data suggest that AngII signaling promotes follicle growth in cattle and does so by regulating genes involved in estradiol secretion and granulosa cell proliferation and differentiation.

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

“…Receptors AT1 and AT2 for ANG have been found in the granulosa cells of the antral follicles and in the primordial primary and secondary follicles of sows (Shuttleworth et al 2002). Administration of an ANG inhibitor in cows avoided the growth of the predominant follicle, and decreased the concentrations of E2 (Ferreira et al 2011). Similarly, in women subjected to ovaric stimulation with human menopausal gonadotropin (HMG), concentrations of ANG were positively correlated with E2 and DPF (Jarry et al 1988).…”

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

“…These two distinct pathways (endocrine and local RAS) may be present in the control of a single physiological event. In the ovary, RAS underlies important ovarian blood pressure control , Acosta et al 2000 and autocrine/paracrine signaling regulating gene expression (Acosta et al 1999, Portela et al 2008, Ferreira et al 2011a. A detailed discussion on the local RAS physiology has been presented by Paul et al (2006).…”

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

“…Similarly, there was no effect on mRNA expression for STAR ( Figure 3C) and the steroidogenic enzymes HDS3B2 ( Figure 3D), CYP11A1 ( Figure 3E) and CYP17A1 ( Figure 3F) between different treatments. These results suggest that Ang II does not regulate steroidogenesis in bovine theca cells during the preovulatory period, such as in follicular deviation, as first shown by FERREIRA et al (2011a) in bovine theca cells treat with saralasin. However, variances in the experimental conditions, such as the reproductive status and metabolism of the cows used for cell collection, might have accounted for the nonhomogenous findings.…”

“…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). Although it seems that Ang II does not stimulate the synthesis of androstenedione and testosterone in theca cells, and progesterone in granulosa cells, it might have a role in estrogen prodution in granulosa cells.…”

“…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). During the preovulatory period, variations in AGTR2 mRNA levels were shown in theca but not in granulosa cells after the administration of analogue GnRH (SIQUEIRA et al, 2012).…”