Abstract
In addition to the classic, endocrine renin-angiotensin system, local renin-angiotensin system (RAS) has been documented in many tissues and organs, including the ovaries. The localization and functional activity of the two opposing axes of the system, viz. ACE1/Ang II/AT1 and ACE2/Ang-(1-7)/MAS1, differs between animal species and varied according to the stage of follicle development. It appears that the angiotensin peptides and their receptors participate in reproductive processes such as folliculogenesis, steroidogenesis, oocyte maturation, and ovulation. In addition, changes in the constituent compounds of local RAS may contribute to pathological conditions, such as polycystic ovary syndrome, ovarian hyperstimulation syndrome, and ovarian cancer. This review article examines the expression, localization, metabolism, and activity of individual elements of the ACE2/Ang-(1-7)/MAS1 axis in the ovaries of various animal species. The manuscript also presents the relationship between the secretion of gonadotropins and sex hormones and expression of Ang-(1-7) and MAS1 receptors. It also summarizes current knowledge regarding the positive and negative impact of ACE2/Ang-(1-7)/MAS1 axis on ovarian function.
Highlights
Ovaries are female gonads responsible for the production of sex cells and the synthesis of hormones necessary for regulation of reproductive functions
Changes in the activity of the local angiotensinangiotensin-converting enzyme 2 (ACE2)/Ang-(1-7)/MAS1 pathway can result in fertility problems through the induction of ovarian diseases [4,5,6,7]
It can hydrolyze Ang II to Ang-(1-7) 10 times more efficiently than PEP and 600 times more so hydrolyze Ang II to Ang-(1-7) 10 times more efficiently than PEP and 600 times more so than than prolyl-carboxypeptidase (PRCP) [11]. These results suggest that the primary role for ACE2 is prolyl-carboxypeptidase (PRCP) [11]. These results suggest that the primary role for ACE2 is the the conversion of Ang II to Ang-(1–7); it is worth noting that Ang-(1-7) and Ang-(1-9) are not cleaved conversion of Ang II to Ang-(1–7); it is worth noting that Ang-(1-7) and Ang-(1-9) are not cleaved by by ACE2
Summary
Ovaries are female gonads responsible for the production of sex cells (oocytes) and the synthesis of hormones necessary for regulation of reproductive functions. The primordial follicles undergo a series of critical histological and hormonal changes, in which cell proliferation, and the differentiation and development of local blood supply, play a key role. These processes are regulated by gonadotropins (LH and FSH), sex steroids, and peptide hormones. Changes in the activity of the local ACE2/Ang-(1-7)/MAS1 pathway can result in fertility problems through the induction of ovarian diseases [4,5,6,7]. The generated nonapeptide can be subsequently hydrolyzed to Ang-(1-7) via via either neprilysin or angiotensin-I-converting enzyme (ACE1). Ang-(1-9) is a 6-fold better either neprilysin or angiotensin-I-converting enzyme (ACE1).
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