Login Register Cart 0
Generic placeholder image

Protein & Peptide Letters

Editor-in-Chief

ISSN (Print): 0929-8665
ISSN (Online): 1875-5305

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe
Letter Article

Angiotensin-(1-7), Angiotensin-Converting Enzyme 2 and Mas Receptor in Rat Polycystic Ovaries

Author(s): Virginia M. Pereira, Fernando M. Reis*, Maíra Casalechi and Adelina M. Reis

Volume 28, Issue 3, 2021

Published on: 26 August, 2020

Page: [249 - 254] Pages: 6

DOI: 10.2174/0929866527666200826104410

Price: $65

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.

« Previous Next »
Graphical Abstract

[1]
Santos, R.A.S.; Sampaio, W.O.; Alzamora, A.C.; Motta-Santos, D.; Alenina, N.; Bader, M.; Campagnole-Santos, M.J. The ACE2/angiotensin-(1-7)/MAS axis of the renin-angiotensin system: Focus on angiotensin-(1-7). Physiol. Rev., 2018, 98(1), 505-553.
[http://dx.doi.org/10.1152/physrev.00023.2016] [PMID: 29351514]
[2]
dos Reis, A.M.; Reis, F.M. Mas and the Reproductive System. In: The Protective Arm of the Renin Angiotensin System (RAS): Functional Aspects and Therapeutic Implications. Unger, T.; Steckelings, U.M.; dos Santos, R.A.S.; Eds., Elsevier, 2015 255-262.
[http://dx.doi.org/10.1016/B978-0-12-801364-9.00036-5]
[3]
Palumbo, A.; Ávila, J.; Naftolin, F. The Ovarian Renin-Angiotensin System (OVRAS): A major factor in ovarian function and disease. Reprod. Sci., 2016, 23(12), 1644-1655.
[http://dx.doi.org/10.1177/1933719116672588] [PMID: 27821561]
[4]
Santos, R.A.; Brosnihan, K.B.; Jacobsen, D.W.; DiCorleto, P.E.; Ferrario, C.M. Production of angiotensin-(1-7) by human vascular endothelium. Hypertension, 1992, 19(2)(Suppl.), II56-II61.
[http://dx.doi.org/10.1161/01.HYP.19.2_Suppl.II56] [PMID: 1310484]
[5]
Pountain, S.J.; Pipkin, F.B.; Hunter, M.G. The ontogeny of components of the renin-angiotensin system in the porcine fetal ovary. Anim. Reprod. Sci., 2010, 117(1-2), 119-126.
[http://dx.doi.org/10.1016/j.anireprosci.2009.03.006] [PMID: 19372013]
[6]
Costa, A.P.; Fagundes-Moura, C.R.; Pereira, V.M.; Silva, L.F.; Vieira, M.A.; Santos, R.A.; Dos Reis, A.M. Angiotensin-(1-7): a novel peptide in the ovary. Endocrinology, 2003, 144(5), 1942-1948.
[http://dx.doi.org/10.1210/en.2002-220787] [PMID: 12697701]
[7]
Viana, G.E.; Pereira, V.M.; Honorato-Sampaio, K.; Oliveira, C.A.; Santos, R.A.; Reis, A.M. Angiotensin-(1-7) induces ovulation and steroidogenesis in perfused rabbit ovaries. Exp. Physiol., 2011, 96(9), 957-965.
[http://dx.doi.org/10.1113/expphysiol.2011.058453] [PMID: 21666031]
[8]
Rocha, A.L.; Oliveira, F.R.; Azevedo, R.C.; Silva, V.A.; Peres, T.M.; Candido, A.L.; Gomes, K.B.; Reis, F.M. Recent advances in the understanding and management of polycystic ovary syndrome. F1000 Res., 2019, 8, 8.
[http://dx.doi.org/10.12688/f1000research.15318.1] [PMID: 31069057]
[9]
Carvalho, L.M.L.; Dos Reis, F.M.; Candido, A.L.; Nunes, F.F.C.; Ferreira, C.N.; Gomes, K.B. Polycystic Ovary Syndrome as a systemic disease with multiple molecular pathways: a narrative review. Endocr. Regul., 2018, 52(4), 208-221.
[http://dx.doi.org/10.2478/enr-2018-0026] [PMID: 31517612]
[10]
Witchel, S.F.; Teede, H.J.; Peña, A.S.; Curtailing, P.C.O.S. Curtailing PCOS. Pediatr. Res., 2020, 87(2), 353-361.
[http://dx.doi.org/10.1038/s41390-019-0615-1] [PMID: 31627209]
[11]
Kelley, A.S.; Smith, Y.R.; Padmanabhan, V. A narrative review of placental contribution to adverse pregnancy outcomes in women with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2019, 104(11), 5299-5315.
[http://dx.doi.org/10.1210/jc.2019-00383] [PMID: 31393571]
[12]
Wang, J.; Wu, D.; Guo, H.; Li, M. Hyperandrogenemia and insulin resistance: The chief culprit of polycystic ovary syndrome. Life Sci., 2019, 236, 116940.
[http://dx.doi.org/10.1016/j.lfs.2019.116940] [PMID: 31604107]
[13]
Gilling-Smith, C.; Willis, D.S.; Beard, R.W.; Franks, S. Hypersecretion of androstenedione by isolated thecal cells from polycystic ovaries. J. Clin. Endocrinol. Metab., 1994, 79(4), 1158-1165.
[PMID: 7962289]
[14]
Jakimiuk, A.J.; Weitsman, S.R.; Navab, A.; Magoffin, D.A. Luteinizing hormone receptor, steroidogenesis acute regulatory protein, and steroidogenic enzyme messenger ribonucleic acids are overexpressed in thecal and granulosa cells from polycystic ovaries. J. Clin. Endocrinol. Metab., 2001, 86(3), 1318-1323.
[PMID: 11238527]
[15]
Nelson, V.L.; Qin, K.N.; Rosenfield, R.L.; Wood, J.R.; Penning, T.M.; Legro, R.S.; Strauss, J.F., III; McAllister, J.M. The biochemical basis for increased testosterone production in theca cells propagated from patients with polycystic ovary syndrome. J. Clin. Endocrinol. Metab., 2001, 86(12), 5925-5933.
[http://dx.doi.org/10.1210/jcem.86.12.8088] [PMID: 11739466]
[16]
Lara, H.E.; Dissen, G.A.; Leyton, V.; Paredes, A.; Fuenzalida, H.; Fiedler, J.L.; Ojeda, S.R. An increased intraovarian synthesis of nerve growth factor and its low affinity receptor is a principal component of steroid-induced polycystic ovary in the rat. Endocrinology, 2000, 141(3), 1059-1072.
[http://dx.doi.org/10.1210/endo.141.3.7395] [PMID: 10698182]
[17]
Parra, C.; Fiedler, J.L.; Luna, S.L.; Greiner, M.; Padmanabhan, V.; Lara, H.E. Participation of vasoactive intestinal polypeptide in ovarian steroids production during the rat estrous cycle and in the development of estradiol valerate-induced polycystic ovary. Reproduction, 2007, 133(1), 147-154.
[http://dx.doi.org/10.1530/rep.1.01214] [PMID: 17244741]
[18]
Pereira, V.M.; Honorato-Sampaio, K.; Martins, A.S.; Reis, F.M.; Reis, A.M. Downregulation of natriuretic peptide system and increased steroidogenesis in rat polycystic ovary. Peptides, 2014, 60, 80-85.
[http://dx.doi.org/10.1016/j.peptides.2014.07.027] [PMID: 25111374]
[19]
Brawer, J.R.; Munoz, M.; Farookhi, R. Development of the polycystic ovarian condition (PCO) in the estradiol valerate-treated rat. Biol. Reprod., 1986, 35(3), 647-655.
[http://dx.doi.org/10.1095/biolreprod35.3.647] [PMID: 3098314]
[20]
Bernardi, F.; Salvestroni, C.; Casarosa, E.; Nappi, R.E.; Lanzone, A.; Luisi, S.; Purdy, R.H.; Petraglia, F.; Genazzani, A.R. Aging is associated with changes in allopregnanolone concentrations in brain, endocrine glands and serum in male rats. Eur. J. Endocrinol., 1998, 138(3), 316-321.
[http://dx.doi.org/10.1530/eje.0.1380316] [PMID: 9539307]
[21]
Bélanger, A.; Caron, S.; Picard, V. Simultaneous radioimmunoassay of progestins, androgens and estrogens in rat testis. J. Steroid Biochem., 1980, 13(2), 185-190.
[http://dx.doi.org/10.1016/0022-4731(80)90190-9] [PMID: 7382493]
[22]
Pereira, V.M.; Reis, F.M.; Santos, R.A.; Cassali, G.D.; Santos, S.H.; Honorato-Sampaio, K.; dos Reis, A.M. Gonadotropin stimulation increases the expression of angiotensin-(1--7) and MAS receptor in the rat ovary. Reprod. Sci., 2009, 16(12), 1165-1174.
[http://dx.doi.org/10.1177/1933719109343309] [PMID: 19703990]
[23]
Pereira, V.M.; Costa, A.P.; Rosa-E-Silva, A.A.; Vieira, M.A.; Reis, A.M. Regulation of steroidogenesis by atrial natriuretic peptide (ANP) in the rat testis: differential involvement of GC-A and C receptors. Peptides, 2008, 29(11), 2024-2032.
[http://dx.doi.org/10.1016/j.peptides.2008.08.005] [PMID: 18778744]
[24]
Simões, E. Silva, A.C.; Diniz, J.S.; Regueira Filho, A.; Santos, R.A. The renin angiotensin system in childhood hypertension: selective increase of angiotensin-(1-7) in essential hypertension. J. Pediatr., 2004, 145(1), 93-98.
[http://dx.doi.org/10.1016/j.jpeds.2004.03.055] [PMID: 15238914]
[25]
Becker, L.K.; Etelvino, G.M.; Walther, T.; Santos, R.A.; Campagnole-Santos, M.J. Immunofluorescence localization of the receptor Mas in cardiovascular-related areas of the rat brain. Am. J. Physiol. Heart Circ. Physiol., 2007, 293(3), H1416-H1424.
[http://dx.doi.org/10.1152/ajpheart.00141.2007] [PMID: 17496218]
[26]
Divyashree, S.; Janhavi, P.; Ravindra, P.V.; Muthukumar, S.P. Experimental models of polycystic ovary syndrome: An update. Life Sci., 2019, 237, 116911.
[http://dx.doi.org/10.1016/j.lfs.2019.116911] [PMID: 31606385]
[27]
Shi, D.; Vine, D.F. Animal models of polycystic ovary syndrome: a focused review of rodent models in relationship to clinical phenotypes and cardiometabolic risk. Fertil. Steril., 2012, 98(1), 185-193.
[http://dx.doi.org/10.1016/j.fertnstert.2012.04.006] [PMID: 22607890]
[28]
Miller, W. L. Disorders in the initial steps of steroid hormone synthesis. J. Steroid. Biochem. Mol. Biol., 2017, 165(Pt A), 18-37.
[29]
Pon, L.A.; Orme-Johnson, N.R. Acute stimulation of steroidogenesis in corpus luteum and adrenal cortex by peptide hormones. Rapid induction of a similar protein in both tissues. J. Biol. Chem., 1986, 261(14), 6594-6599.
[PMID: 3009462]
[30]
Selvaraj, V.; Stocco, D.M.; Clark, B.J. Current knowledge on the acute regulation of steroidogenesis. Biol. Reprod., 2018, 99(1), 13-26.
[http://dx.doi.org/10.1093/biolre/ioy102] [PMID: 29718098]
[31]
Manenda, M.S.; Hamel, C.J.; Masselot-Joubert, L.; Picard, M.E.; Shi, R. Androgen-metabolizing enzymes: A structural perspective. J. Steroid Biochem. Mol. Biol., 2016, 161, 54-72.
[http://dx.doi.org/10.1016/j.jsbmb.2016.02.021] [PMID: 26924584]
[32]
Astapova, O.; Minor, B.M.N.; Hammes, S.R. Physiological and pathological androgen actions in the ovary. Endocrinology, 2019, 160(5), 1166-1174.
[http://dx.doi.org/10.1210/en.2019-00101] [PMID: 30912811]
[33]
Sidra, S.; Tariq, M.H.; Farrukh, M.J.; Mohsin, M. Evaluation of clinical manifestations, health risks, and quality of life among women with polycystic ovary syndrome. PLoS One, 2019, 14(10), e0223329.
[http://dx.doi.org/10.1371/journal.pone.0223329] [PMID: 31603907]
[34]
Zhou, P.; Yang, X.L.; Wang, X.G.; Hu, B.; Zhang, L.; Zhang, W.; Si, HR.; Zhu, Y.; Li, B.; Huang, C. L.; Chen, H.D.; Chen, J.; Luo, Y.; Guo, H.; Jiang, R. D.; Liu, M.Q.; Chen, Y.; Shen, X.R.; Wang, X.; Zheng, X.S.; Zhao, K.; Chen, Q. J.; Deng, F.; Liu, L.L.; Yan, B.; Zhan, F.X.; Wang, Y.Y.; Xiao, G. F.; Shi, Z.L. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature, 2020, 579(7798), 270-273.
[35]
Lu, R.; Zhao, X.; Li, J.; Niu, P.; Yang, B.; Wu, H.; Wang, W.; Song, H.; Huang, B.; Zhu, N.; Bi, Y.; Ma, X.; Zhan, F.; Wang, L.; Hu, T.; Zhou, H.; Hu, Z.; Zhou, W.; Zhao, L.; Chen, J.; Meng, Y.; Wang, J.; Lin, Y.; Yuan, J.; Xie, Z.; Ma, J.; Liu, W. J.; Wang, D.; Xu, W.; Holmes, E.C.; Gao, G.F.; Wu, G.; Chen, W.; Shi, W.; Tan, W. Genomic characterisation and epidemiology of 2019 novel coronavirus: implications for virus origins and receptor binding. Lancet, 2020, 395(10224), 565-574.
[36]
Beigmohammadi, M.T.; Jahanbin, B.; Safaei, M.; Amoozadeh, L.; Khoshavi, M.; Mehrtash, V.; Jafarzadeh, B.; Abdollahi, A. Pathological findings of postmortem biopsies from lung, heart, and liver of 7 deceased COVID-19 patients. Int. J. Surg. Pathol., 2020. [Online ahead of print]
[37]
Pan, F.; Ye, T.; Sun, P.; Gui, S.; Liang, B.; Li, L.; Zheng, D.; Wang, J.; Hesketh, R. L.; Yang, L.; Zheng, C. Time course of lung changes at chest CT during recovery from coronavirus disease 2019 (COVID-19). Radiology, 2020, 295(3), 715-721.
[38]
Cavallo, I.K.; Dela Cruz, C.; Oliveira, M.L.; Del Puerto, H.L.; Dias, J.A.; Lobach, V.N.; Casalechi, M.; Camargos, M.G.; Reis, A.M.; Santos, R.A.; Reis, F.M. Angiotensin-(1-7) in human follicular fluid correlates with oocyte maturation. Hum. Reprod., 2017, 32(6), 1318-1324.
[39]
Racilan, A.M.; Assis, W.A.; Casalechi, M.; Spagnolo-Souza, A.; Pascoal-Xavier, M.A.; Simões-e-Silva, A. C.; Del Puerto, H.L.; Reis, F.M. Angiotensin-converting enzyme 2, the SARS-CoV-2 cellular receptor, is widely expressed in human myometrium and uterine leiomyoma. J. Endometr. Pelvic Pain Disord., 2021, 13(1), 20-24.
[40]
Jing, Y.; Run-Qian, L.; Hao-Ran, W.; Hao-Ran, C.; Ya-Bin, L.; Yang, G.; Fei, C. Potential influence of COVID-19/ACE2 on the female reproductive system. Mol. Hum. Reprod., 2020, 26(6), 367-373.

Rights & Permissions Print Cite
Article Metrics
37
1
© 2024 Bentham Science Publishers | Privacy Policy