Angiotensin-(1-7) induces ovulation and steroidogenesis in perfused rabbit ovaries

Abstract

A local renin-angiotensin system has been described in several organs, including the ovary; however, data indicating a role for angiotensin II in the induction of ovulation are controversial. We have previously shown the presence of a novel peptide, angiotensin-(1-7) [Ang-(1-7)], in the rat ovary and its effect on steroidogenesis. The objective of the present study was to determine whether Ang-(1-7) plays a role in ovulation. We first determined the presence and distribution of Ang-(1-7) and the receptor Mas in rabbit ovaries by immunohistochemistry. Angiotensin-(1-7) and Mas immunoreactivity were observed in interstitial cells and oocytes of immature ovaries. Immunoreactivity for Ang-(1-7) and Mas was also observed in theca and granulosa cells of preovulatory follicles in ovaries of gonadotrophin-stimulated rabbits. To verify the effect of Ang-(1-7) in ovulation and steroidogenesis, we used isolated ovaries from immature rabbits pretreated with equine chorionic gonadotrophin (50 i.u., 48 h before the experiment) and then perfused in vitro. The ovulatory efficiency was determined by the number of oocytes compared with the number of preovulatory follicles present in the ovary. Angiotensin-(1-7) stimulated oestradiol production and enhanced ovulatory efficiency, which was blocked by the specific Ang-(1-7) antagonist, A-779. Ovulation induced by human chorionic gonadotrophin was also antagonized by A-779. These results show, for the first time, the involvement of a novel regulatory peptide system, Ang-(1-7) and Mas, in the ovulatory process. More importantly, because A-779 antagonized hCG-induced ovulation, it may be inferred that Ang-(1-7) plays an important role in ovulation, possibly as a mediator of gonadotrophin action.

Mas and Its Related G Protein–Coupled Receptors, Mrgprs

“…It is also involved in ovulation in rabbits (Viana et al, 2011). Moreover, the Mas antagonist A-779 inhibited the germinal vesicle breakdown induced by Ang-(1-7) and reduced oocyte maturation stimulated by luteinizing hormone , further corroborating the role of Mas in female reproduction.…”

International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

“…MAS gene expression was reported in human ovaries . Both Ang (1)(2)(3)(4)(5)(6)(7) and MAS modulate folliculogenesis, ovulation, and pregnancy (Viana et al, 2011).…”

Effects of Estradiol on the Paracrine Regulator Expression of In Vitro Maturated Murine Ovarian Follicles

“…As autocrine/paracrine regulator, it has been known to be involved in the ovarian follicular development since the existence of prorenin, renin, angiotensinogen, angiotensinconverting enzyme, AT and its receptors were identified in the ovary. This ovarian renin-angiotensin system (RAS) plays an important role in such dimensions of ovarian follicular physiology as follicular development, steroidogenesis [18], oocyte maturation [19] and ovulation [20] through its receptors on granulosa cells. Its concentration increased in the follicular fluid of the dominant follicle [21].…”