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Tissue specific localization of angiotensin-(1–7) and its receptor Mas in the uterus of ovariectomized rats

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Abstract

The vasoactive peptide angiotensin (Ang)-(1–7) has vasodilator, antifibrotic and antihypertrophic properties, but little is known about its regulation in the uterus. The aim of this study was to evaluate Ang-(1–7) and its receptor Mas expression throughout rat uterine tissues, in ovariectomized animals treated with estrogen alone or combined with progestin. Adult Wistar rats (n = 19) were ovariectomized and randomly assigned into three different groups 1 week later. One group received a single dose of estradiol benzoate (1.5 mg/kg, i.m. injection, n = 6). Another group received estradiol associated with depot medroxyprogesterone acetate (3 mg/kg, i.m. injection, n = 6). Control group (n = 7) received oil injection. One week later, the rats were euthanized and their uteri were fixed and stained by immunohistochemistry, using a polyclonal antibody specific to Ang-(1–7) and its receptor Mas. Ang-(1–7) was detected in all uterine tissues, but it was weak or absent in the circular myometrium of treated animals. The intensity of the immunostaining decreased in the glandular epithelium of hormonally treated animals when compared to controls. In estrogen treated rats, Ang-(1–7) labeling was scattered and sometimes included the nuclei of glandular cells. We also detected Ang-(1–7) expression in longitudinal myometrium and uterine serosa. Mas receptor was present in all tissues with similar intensity among the tissue types in the control and estrogen plus progestin groups. In the estrogen group, Mas staining was stronger in the luminal and glandular epithelium when compared with stroma or circular myometrium. In conclusion, ovarian steroids are not required to allow endometrial expression of Ang-(1–7) and its receptor Mas in rats, as it remains abundant in ovariectomized animals. However, estrogen and progestin may modulate the distribution pattern of this peptide in the endometrium, especially in the glandular compartment.

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References

  • Ahmed A, Li XF, Shams M, Gregory J, Rollason T, Barnes NM, Newton JR (1995) Localization of the angiotensin II and its receptor subtype expression in human endometrium and identification of a novel high-affinity angiotensin II binding site. J Clin Invest 96:848–857. doi:10.1172/JCI118131

    Article  PubMed  CAS  Google Scholar 

  • Baker KM, Aceto JF (1990) Angiotensin II stimulation of protein synthesis and cell growth in chick heart cells. Am J Physiol Heart Circ Physiol 259:H610–H618

    CAS  Google Scholar 

  • Brosnihan KB, Bharadwaj MS, Yamaleyeva LM, Neves LA (2012) Decidualized pseudopregnant rat uterus shows marked reduction in Ang II and Ang-(1–7) levels. Placenta 33:17–23. doi:10.1016/j.placenta.2011.10.016

    Article  PubMed  CAS  Google Scholar 

  • Campbell DJ, Habener JF (1986) Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat. J Clin Investig 78:31–39. doi:10.1172/JCI112566

    Article  PubMed  CAS  Google Scholar 

  • Costa AP, Fagundes-Moura CR, Pereira VM, Silva LF, Vieira MA, Santos RA, Dos Reis AM (2003) Angiotensin-(1–7): a novel peptide in the ovary. Endocrinology 144:1942–1948. doi:10.1210/en.2002-220787

    Article  PubMed  CAS  Google Scholar 

  • Cunningham FG, Williams JW, Leveno KJ, Bloom S, Hauth JC, Rouse DJ (2010) Parturition. In: Cunningham FG, Leveno KJ, Hauth JC, Rouse DJ (eds) Williams obstetrics, 23rd edn. McGraw-Hill Medical, New York, pp 136–173

    Google Scholar 

  • Daemen MJ (1991) Angiotensin II induces smooth muscle cell proliferation in the normal and injured rat arterial wall. Circ Res 68:450–456

    Article  PubMed  CAS  Google Scholar 

  • Deliu E, Tica AA, Motoc D, Brailoiu GC, Brailoiu E (2011) Intracellular angiotensin II activates rat myometrium. Am J Physiol Cell Physiol 301:559–565. doi:10.1152/ajpcell.00123.2011

    Article  Google Scholar 

  • Dimmeler S, Rippmann V, Weiland U, Haendeler J, Zeiher AM (1997) Angiotensin II induces apoptosis of human endothelial cells. Protective effect of nitric oxide. Circ Res 81:970–976. doi:10.1161/01.RES.81.6.970

    Article  PubMed  CAS  Google Scholar 

  • Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, Donovan M, Woolf B, Robison K, Jeyaseelan R, Breitbart RE, Acton S (2000) A novel angiotensin converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin-(1–9). Circ Res 87:e1–e9. doi:10.1161/01.RES.87.5.e1

    Article  PubMed  CAS  Google Scholar 

  • Ferreira MC, Cavallo IK, Florio P, Petraglia F, Reis FM (2008) Activin betaA subunit, follistatin and follistatin-like 3 are expressed in the endometrium of ovariectomized rats and regulated by estrogen replacement. J Mol Histol 39:535–541. doi:10.1007/s10735-008-9194-x

    Article  PubMed  CAS  Google Scholar 

  • Gwathmey TM, Westwood BM, Pirro NT, Tang L, Rose JC, Diz DI, Chappell MC (2010) Nuclear angiotensin-(1–7) receptor is functionally coupled to the formation of nitric oxide. Am J Physiol Renal Physiol 299:983–990. doi:10.1152/ajprenal.00371.2010

    Article  Google Scholar 

  • Hackenthal E, Metz J, Poulsen K, Rix E, Taugner R (1980) Renin in the uterus of non-pregnant mice. Immunocytochemical, ultrastructural and biochemical studies. Histochemistry 66:229–238. doi:10.1007/BF00495736

    Article  PubMed  CAS  Google Scholar 

  • Hsueh AJ, Peck EJ Jr, Clark JH (1976) Control of uterine estrogen receptor levels by progesterone. Endocrinology 98:438–444

    Article  PubMed  CAS  Google Scholar 

  • Li XF, Ahmed A (1997) Compartmentalization and cyclic variation of immunoreactivity of renin and angiotensin converting enzyme in human endometrium throughout the menstrual cycle. Hum Reprod 12:2804–2809. doi:10.1093/humrep/12.12.2804

    Article  PubMed  CAS  Google Scholar 

  • Neves LA, Stovall K, Joyner J, Valdés G, Gallagher PE, Ferrario CM, Merrill DC, Brosnihan KB (2008) ACE2 and ANG-(1–7) in the rat uterus during early and late gestation. Am J Physiol Regul Integr Comp Physiol 294:151–161. doi:10.1152/ajpregu.00514.2007

    Article  Google Scholar 

  • Pandey KN, Misono KS, Inagami T (1984) Evidence for intracellular formation of angiotensins: coexistence of renin and angiotensin-converting enzyme in Leydig cells of rat testis. Biochem Biophys Res Commun 122(3):1337–1343

    Google Scholar 

  • Pawlikowski M, Meleń-Mucha G, Mucha S (1999) The involvement of the renin-angiotensin system in the regulation of cell proliferation in the rat endometrium. Cell Mol Life Sci 55:506–510. doi:1420-682X:99:030506-05

    Article  PubMed  CAS  Google Scholar 

  • Pereira VM, Reis FM, Santos RA, Cassali GD, Santos SH, Honorato-Sampaio K, dos Reis AM (2009) Gonadotropin stimulation increases the expression of angiotensin-(1–7) and MAS receptor in the rat ovary. Reprod Sci 16:1165–1174. doi:10.1177/1933719109343309

    Article  PubMed  CAS  Google Scholar 

  • Santos RA, Ferreira AJ, Simões E Silva AC (2008) Recent advances in the angiotensin-converting enzyme 2-angiotensin(1–7)-Mas axis. Exp Physiol 93(5):519–527

    Google Scholar 

  • Shah DM, Higuchi K, Inagami T, Osteen KG (1991) Effect of progesterone on renin secretion in endometrial stromal, chorionic trophoblast, and mesenchymal monolayer cultures. Am J Obstet Gynecol 164:1145–1150

    PubMed  CAS  Google Scholar 

  • Simões e Silva AC, Diniz JSS, Filho AR, Santos RAS (2004) The renin angiotensin system in childhood hypertension: selective increase of angiotensin-(1–7) in essential hypertension. J Pediatr 145:93–98. doi:10.1016/j.jpeds.2004.03.055

    Article  PubMed  Google Scholar 

  • Squires PM, Kennedy TG (1992) Evidence for a role for a uterine renin-angiotensin system in decidualization in rats. J Reprod Fertil 95:791–802. doi:10.1530/jrf.0.0950791

    Article  PubMed  CAS  Google Scholar 

  • Tang SS, Rogg H, Schumacher R, Dzau VJ (1992) Characterization of nuclear angiotensin-II-binding sites in rat liver and comparison with plasma membrane receptors. Endocrinology 131:374–380. doi:10.1210/en.131.1.374

    Article  PubMed  CAS  Google Scholar 

  • Tonnaer JA, Engels GM, Wiegant VM, Burbach JP, De Jong W, De Wied D (1983) Proteolytic conversion of angiotensins in rat brain tissue. Eur J Biochem 15(131):415–421. doi:10.1111/j.1432-1033.1983.tb07279.x

    Article  Google Scholar 

  • Vaz-Silva J, Carneiro MM, Ferreira MC, Pinheiro SV, Silva DA, Silva-Filho AL, Witz CA, Reis AM, Santos RA, Reis FM (2009) The vasoactive peptide angiotensin-(1–7), its receptor Mas and the angiotensin-converting enzyme type 2 are expressed in the human endometrium. Reprod Sci 16:247–256. doi:10.1177/1933719108327593

    Article  PubMed  CAS  Google Scholar 

  • Yoshimura Y (1997) The ovarian renin-angiotensin system in reproductive physiology. Front Neuroendocrinol 18:247–291. doi:10.1006/frne.1997.0152

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was support by grants from the Brazilian National Institute of Hormones and Women’s Health, and Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil.

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Correspondence to Fernando M. Reis.

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Vaz-Silva, J., Tavares, R.L., Ferreira, M.C. et al. Tissue specific localization of angiotensin-(1–7) and its receptor Mas in the uterus of ovariectomized rats. J Mol Hist 43, 597–602 (2012). https://doi.org/10.1007/s10735-012-9427-x

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