Abstract
Background: Hyperandrogenism is a pivotal mediator in the pathogenesis of the polycystic ovary syndrome (PCOS), but the mechanisms of androgen excess in this condition are not fully understood. Angiotensin (Ang)-(1-7) is an active peptide of the renin-angiotensin system (RAS) that stimulates ovarian follicular growth and testosterone release in vitro.
Objective: To investigate whether Ang-(1-7), its receptor Mas and angiotensin-converting enzyme 2 (ACE2), the enzyme that converts Ang II into Ang-(1-7), are expressed in rat polycystic ovaries (PCO) and thus if this peptide system might be associated with excess androgen production in PCO. Methods: A rat model that shares some features of PCOS such as disruption of folliculogenesis and multiple ovarian cyst formation was used in the study. Results: We found reduced levels of Ang-(1-7) and Mas receptor in PCO compared to normal ovaries. Also, ACE2 mRNA expression was reduced in PCO compared to ovaries of control rats (p < 0.05). PCO had high levels of estrogen and testosterone and increased mRNA for upstream enzymes of the steroidogenic cascade, but not of P450 aromatase. Conclusion: These findings suggest that the ovarian ACE2-Ang-(1-7)-Mas receptor axis is inhibited and therefore may not be a co-factor of excess testosterone production in rat PCO.Keywords: Angiotensin-(1-7), mas receptor, ovary, steroidogenesis, PCOs, renin-angiotensin system.
Graphical Abstract
[http://dx.doi.org/10.1152/physrev.00023.2016] [PMID: 29351514]
[http://dx.doi.org/10.1016/B978-0-12-801364-9.00036-5]
[http://dx.doi.org/10.1177/1933719116672588] [PMID: 27821561]
[http://dx.doi.org/10.1161/01.HYP.19.2_Suppl.II56] [PMID: 1310484]
[http://dx.doi.org/10.1016/j.anireprosci.2009.03.006] [PMID: 19372013]
[http://dx.doi.org/10.1210/en.2002-220787] [PMID: 12697701]
[http://dx.doi.org/10.1113/expphysiol.2011.058453] [PMID: 21666031]
[http://dx.doi.org/10.12688/f1000research.15318.1] [PMID: 31069057]
[http://dx.doi.org/10.2478/enr-2018-0026] [PMID: 31517612]
[http://dx.doi.org/10.1038/s41390-019-0615-1] [PMID: 31627209]
[http://dx.doi.org/10.1210/jc.2019-00383] [PMID: 31393571]
[http://dx.doi.org/10.1016/j.lfs.2019.116940] [PMID: 31604107]
[PMID: 7962289]
[PMID: 11238527]
[http://dx.doi.org/10.1210/jcem.86.12.8088] [PMID: 11739466]
[http://dx.doi.org/10.1210/endo.141.3.7395] [PMID: 10698182]
[http://dx.doi.org/10.1530/rep.1.01214] [PMID: 17244741]
[http://dx.doi.org/10.1016/j.peptides.2014.07.027] [PMID: 25111374]
[http://dx.doi.org/10.1095/biolreprod35.3.647] [PMID: 3098314]
[http://dx.doi.org/10.1530/eje.0.1380316] [PMID: 9539307]
[http://dx.doi.org/10.1016/0022-4731(80)90190-9] [PMID: 7382493]
[http://dx.doi.org/10.1177/1933719109343309] [PMID: 19703990]
[http://dx.doi.org/10.1016/j.peptides.2008.08.005] [PMID: 18778744]
[http://dx.doi.org/10.1016/j.jpeds.2004.03.055] [PMID: 15238914]
[http://dx.doi.org/10.1152/ajpheart.00141.2007] [PMID: 17496218]
[http://dx.doi.org/10.1016/j.lfs.2019.116911] [PMID: 31606385]
[http://dx.doi.org/10.1016/j.fertnstert.2012.04.006] [PMID: 22607890]
[PMID: 3009462]
[http://dx.doi.org/10.1093/biolre/ioy102] [PMID: 29718098]
[http://dx.doi.org/10.1016/j.jsbmb.2016.02.021] [PMID: 26924584]
[http://dx.doi.org/10.1210/en.2019-00101] [PMID: 30912811]
[http://dx.doi.org/10.1371/journal.pone.0223329] [PMID: 31603907]