The renin–angiotensin system is well known as a systemic endocrine pathway that regulates blood pressure and salt–water metabolism. In addition to the systemic renin–angiotensin system there is evidence in different species for the presence of a local tissue renin–angiotensin system, which allows local production of the bioactive peptides angiotensin II and angiotensin (1-7). The local renin–angiotensin system has been found in a variety of tissues including tissue of the human reproductive tract. Thus, it was suspected that it may have important functions in the local hormonal microenvironment. Here, a systematic literature search was undertaken to review whether there is evidence for regulatory functions of the local tissue renin–angiotensin system in the human reproductive tract under physiological and pathological conditions.
AntonLBrosnihanKB (2008) Systemic and uteroplacental renin–angiotensin system in normal and pre-eclamptic pregnancies. Ther Adv Cardiovasc Dis2: 349–362.
2.
AntonLMerillDCNevesLADizDICorthornJValdesG. (2009) The uterine placental bed renin–angiotensin system in normal and preeclamptic pregnancy. Endocrinology150: 4316–4325.
3.
AgerELChongWWWenSWChristophiC (2010) Targeting the angiotensin II type 2 receptor in colorectal liver metastases. Cancer Cell International28: 10–19.
4.
AhmedALiXFShamsMGregoryJRollasonTBarnesNM (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 Invest96: 848–857.
5.
BakerPNBroughton PipkinFSymondsEM (1992) Comparative study of platelet angiotensin II binding and the angiotensin II sensitivity test as predictors of pregnancy-induced hypertension. Clin Sci (Lond)83: 89–95.
6.
Brunswig-SpickenheierBMukopadhayAK (2003) Local regulatory factors in regulation of ovary function: role of prorenin–renin–angiotensin system. Indian J Exp Biol41: 669–681.
7.
BokalEVVrotecHMVirant KlunIVerdenikI (2005) Prolonged HCG action affects angiogenic substances and improves follicular maturation, oocyte quality and fertilization competence in patients with polycystic ovary syndrome. Hum Reprod20: 1562–1568.
8.
CareyRMSiragyHM (2005) Newly recognized components of the renin–angiotensin system: potential role in cardiovascular and renal regulation. Endocr Rev24: 261–271.
9.
Castro-ChavezPCerqueiraRPintalhaoMLeite-MoreiraAF (2010) New pathways of the renin–angiotensin system: the role of ACE2 in cardiovascular pathophysiology and therapy. Expert Opin Ther Targets14(5): 485–496.
10.
ChappellMC (2007) Emerging evidence for a functional angiotensin-converting enzyme 2–angiotensin-(1–7)–MAS receptor axis: more than regulation of blood pressure?Hypertension50(4): 596–9.
11.
ChappellSMorganL (2006) Searching for genetic clues to the causes of pre-eclampsia. Clin Sci (Lond)110: 443–458.
12.
ClereNCorreIFaureSGuihotALVessièresEChalopinM. (2010) Deficiency or blockade of angiotensin II type 2 receptor delays tumorigenesis by inhibiting malignant cell proliferation and angiogenesis. Int J Cancer127: 2279–2291.
13.
CooperACRobinsonGVinsonGPCheungWTBroughton-PipkinF (1999) The localization and expression of the renin–angiotensin system in the human placenta throughout pregnancy. Placenta20: 467–474.
14.
CoxBEWordRARosenfieldCR (1996) Angiotensin II receptor characteristics and subtype expression in uterine arteries and myometrium during pregnancy. J Clin Endocrinol Metab81: 49–58.
15.
CushmanDWOndettoMA (1980) Inhibitors of angiotensin-converting enzyme for treatment of hypertension. Biochem Pharmacol29: 1871–1877.
16.
DanilczykUPenningerJM (2006) Angiotensin-converting enzyme II in the heart and kidney. Circ Res98: 463–471.
17.
DavisJSRuedaBRSpanel-BorowskiK (2003) Microvascular endothelial cells of the corpus luteum. Reprod Biol Endocrinol1: 89.
18.
De GasparoMWhitebreadSKalangaMKDe HertoghRCrevoisierPThomasK (1994) Down regulation of the angiotensin II receptor subtype AT2 in human myometrium during pregnancy. Regul Pept53: 39–45.
19.
De La Chica-RodriguezSCortes-DeniaPRamirez-ExpositoMJDe SaavedraJMSanchez-AgestaR. (2007) Doxazosin blockade of alpha 1-adrenergic receptors increases rat serum progesterone levels: a putative role of ovarian angiotensin III in steroidogenesis. Fertil Steril88: 1071–1075.
20.
DeshayesFNahmiasC (2005) Angiotensin receptors: a new role in cancer?Trends Endocrinol Metab16: 293–299.
21.
DzauVJBernsteinKCelermajerDCohenJDahlöfBDeanfieldJ. (2002) Pathophysiologic and therapeutic importance of tissue ACE: a consensus report. Cardiovasc Drugs Ther16: 149–160.
22.
ErmanAChen-GalBVan DijkDJSulkesJKaplanBBonerG. (1996) Ovarian angiotensin-converting enzyme activity in humans: relationship to estradiol, age, and uterine pathology. J Clin Endocrinol Metab81: 1104–1107.
23.
FerreiraROliveiraJFFernandesRMoraesJFGoncalvesPB (2007) The role of angiotensin II in the early stages of bovine ovulation. Reproduction134: 713–719.
24.
Freitas-SilvaMPereiraDCoelhoCBichoMLopesCMedeirosR (2004) Angiotensin I converting enzyme gene insertion/deletion polymorphism and endometrial human cancer in normotensive and hypertensive women. Cancer Genet Cytogenet155: 42–46.
25.
GiomettiICBertagnolliACOrnesRCDa CostaLFCarambulaSFReisAM. (2005) Angiotensin II reverses the inhibitory action produced by theca cells on bovine oocyte nuclear maturation. Theriogenology63: 1014–1025.
26.
HassaECreatsasGMastorakosGMichalasS (2000) Clinical implication of the ovarian/endometrial renin–angiotensin-aldosterone system. Ann N Y Acad Sci900: 107–118.
27.
HayashiKMiyamotoABerishaBKosmannMROkudaKSchamsD (2000) Regulation of angiotensin II production and angiotensin receptors in microvascular endothelial cells from bovine corpus luteum. Biol Reprod62: 162–167.
28.
HerrDDuncanWCHackGKonradRKreienbergRWulffC (2010) Regulated expression of the renin–angiotensin system in human granulosa lutein cells: angiotensin II increases VEGF expression but its synthesis is reduced by hCG. Arch Gynecol Obstet281: 409–416.
29.
HerrDRodewaldMFraserHMHackGKonradRKreienbergR. (2008) Regulation of endothelial proliferation by the renin–angiotensin system in human umbilical vein endothelial cells. Reproduction136: 125–130.
30.
HerseFDechendRHarsemNKWallukatGJannkeJQuadriF. (2007) Dysregulation of the circulating and tissue based renin–angiotensin system in preeclampsia. Hypertension49: 604–611.
31.
InoKShibataKKajiyamaHYamamotoENagasakaTNawaA. (2006) Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival. Br J Cancer94: 552–560.
32.
ItoMItakuraAOhnoYNomuraMSengaTNagasakaT. (2002) Possible activation of the renin–angiotensin system in the feto–placental unit in preeclampsia. J Clin Endocrinol Metab87: 1871–1878.
33.
KalengaMKDe HertoghRWhitebreadSVankriekenLThomasKde GasparoM (1991) Distribution of the concentrations of angiotensin II (A II), A II receptors, hPL, prolactin, and steroids in human fetal membranes. Rev Fr Gynecol Obstet86: 585–591.
34.
KalengaMKThomasKde GasparoMDe HertoghR (1996) Determination of renin, angiotensin converting enzyme and angiotensin II levels in human placenta, chorion and amnion from women with pregnancy induced hypertension. Clin Endocrinol44: 429–433.
35.
KasumM (2010) New insights in mechanism for development of ovarian hyperstimulation syndrome. Coll Antropol34: 1139–1143.
36.
KnockGASullivanMHMcCarthyAElderMGPolakJMWhartonJ (1994) Angiotensin II (AT1) vascular binding sites in human placentae from normal-term, preeclamptic and growth retarded pregnancies. J Pharmacol Exp Ther271: 1007–1015.
37.
KobayashiSAcostaTJOzawaTHayashiKBerishaBOhtaniM. (2002) Intraluteal release of angiotensin II and progesterone in vivo during corpora lutea development in the cow: effect of vasoactive peptides. Biol Reprod66: 174–179.
38.
LaskowskaMLeszczynsak-GorzelakBOleszczukJ (2003) Placental angiotensin II receptor AT1R in normotensive patients and its correlation between infant birth weight. Eur J Obstet Gynecol Reprod Biol109: 166–170.
39.
LiCAnsariRYuZShahD (2000) Definitive molecular evidence of renin–angiotensin system in human uterine decidual cells. Hypertension36: 159–164.
40.
LiXShamsMZhuJKhaligAWilkesMWhittleM. (1998) Cellular localization of AT1 receptor mRNA and protein in normal placenta and its reduced expression in intrauterine growth restriction. Angiotensin II stimulates the release of vasorelaxants. J Clin Invest101: 442–454.
41.
LiXFAhmedA (1996) Dual role of angiotensin II in the human endometrium. Hum Reprod11: 95–108.
42.
LiXFAhmedA (1997) Compartmentalization and cyclic variation of immunoreactivity of renin and angiotensin converting enzyme in human endometrium throughout the menstrual cycle. Hum Reprod12: 2804–2809.
43.
LiYHJiaoLHLiuRHChenXLWangHWangWH (2004) Localization of angiotensin II in pig ovary and its effects on oocyte maturation in vitro. Theriogenology61: 447–459.
44.
MatsumotoTSagawaNMukoyamaMTanakaIItohHGotoM. (1996) Type 2 angiotensin II receptor is expressed in human myometrium and uterine leiomyoma and is down-regulated during pregnancy. J Clin Endocrinol Metab81: 4366–4372
45.
MorganTCravenCNelsonLLalouelJMWardK (1997) Angiotensinogen T235 expression is elevated in decidual spiral arteries. J Clin Invest100: 1406–1415.
46.
MulrowPJ (1999) Angiotensin II and aldosterone regulation. Regul Pept80: 27–32.
47.
MulrowPJFranco-SaenzR (1996) The adrenal renin–angiotensin system - a local hormonal regulator of aldosterone production. J Hypertension14: 173–176.
48.
NevesLAStovallKJoynerJValdesGGallagherPEFerrarioCM. (2007) ACE2 and Ang-(1–7) in the uterus during early and late gestation. Am J Physiol Regul Integr Comp Physiol294: R151–R161.
49.
NevesLAStovallKJoynerJValdesGGallagherPEFerrarioCM. (2008) ACE 2 and ANG-(1–7) in the rat uterus during early and late gestation. Am J Physiol Regul Integr Comp Physiol294: 151–161.
50.
NielsenAHSchauserKHPoulsenK (2000) Current topic: The uteroplacental renin–angiotensin system. Placenta21: 468–477.
51.
ObermüllerNGentiliMGauerSGretzNWeigelMGeigerH. (2004) Immunohistochemical and mRNA localization of the angiotensin II receptor subtype 2 (AT2) in follicular granulosa cells of the rat ovary. J Histochem Cytochem52: 545–548.
52.
PawlikowskiMMelen-MuchaGMuchaS (1999) The involvement of the renin–angiotensin system in the regulation of cell proliferation in the rat endometrium. Cell Mol Life Sci55: 506–510.
53.
PeachMJ (1977) Renin–angiotensin system: biochemistry and mechanisms of action. Physiol Rev57: 313–370.
54.
PereiraVMReisFMSantosRACassaliGDSantosSHHonorato-SampaioK. (2009) Gonadotropin stimulation increases the expression of angiotensin (1–7) and MAS receptor in the rat ovary. Reprod Sci16: 1165–1176.
55.
PetitAGeoffroyPBelisleS (1996) Expression of angiotensin II type-I receptor and phospholipase C-linked G alpha q/11 protein in the human placenta. J Soc Gynecol Investig3: 316–321.
56.
PountainSJPipkinFBHunterMG (2010) The otogeny of components of the renin–angiotensin system in the porcine fetal ovary. Anim Reprod Sci117: 119–126.
57.
ReisFMBouissouDRPereiraVMCamargosAFDos ReisAMSantosRA (2011) Angiotensin-(1–7), its receptor Mas, and the angiotensin-converting enzyme type 2 are expressed in the human ovary. Fertil Steril95: 176–181.
58.
RizzoAMinoiaGTrisoliniCMutinatiMSpedicatoMMancaR. (2009) Renin and ovarian vascularization in cows with follicular cysts after epidural administration of a GnRH analogue. Anim Reprod Sci116: 226–232.
59.
SaridoganEDjahanbakhchOPuddefootJRDemotroulisCDawdaRHallAJ. (1996) Type 1 angiotensin II receptors in human endometrium. Mol Hum Reprod2: 659–664.
60.
SchamsDBerishaBNeuviansTAmselgruberWKraetzlWD (2003) Real-time changes of the local vasoactive peptide systems (angiotensin, endothelin) in the bovine corpus luteum after induced luteal regression. Mol Reprod Dev65: 57–66.
61.
SchauserKHNielsonAHDantzerVPoulsenK (2001a) Angiotensin-converting enzyme activity in the bovine uteroplacental unit changes in relation to the cycle and pregnancy. Placenta22: 852–862.
62.
SchauserKHNielsenAHWintherHDantzerVPoulsenK (2001b) Localization of the renin–angiotensin system in the bovine ovary: cyclic variation of the angiotensin II receptor expression. Biol Reprod65: 1672–1680.
63.
SchindlerCBramlagePKirchWFerrarioCM (2007) Role of the vasodilator peptide angiotensin-(1–7) in cardiovascular drug therapy. Vasc Health Risk Manag3: 125–137.
ShahDHiguchiKInagamiTOsteenK (1991) Effect of progesterone on renin secretion in endometrial stromal, chorionic trophoblast, and mesenchymal monolayer cultures. Am J Obstet Gynecol164: 1145–1150.
66.
ShibataKKikkawaFMizokamiYKajiyamaHInoKNomuraS. (2005) Possible involvement of adipocyte derived leucine aminopeptidase via angiotensin II in endometrial carcinoma. Tumour Biol26: 9–16.
67.
SinghHJRahmanALarmieETNilaA (2004) Raised prorenin and renin concentrations in pre-eclamptic placentae when measured after acid activation. Placenta25: 631–636.
68.
SipahiIDebanneSMRowlandDYSimonDIFangJC (2010) Angiotensin-receptor blockade and risk of cancer: meta-analysis of randomized controlled trials. Lancet Oncol11: 627–636.
69.
SuganumaTInoKShibataKKajiyamaHNagasakaTMizutaniS. (2005) Functional expression of the angiotensin II type 1 receptor in human ovarian carcinoma and its blockade therapy resulting in suppression of tumor invasion, angiogenesis, and peritoneal dissemination. Clin Cancer Res11: 2686–2694.
70.
SullivanJARupnowHLCaleJMMagnessRRBirdIM (2005) Pregnancy and ovarian steroid regulation of angiotensin II type 1 and type 2 receptor expression in ovarian uterine artery endothelium and vascular smooth muscle. Endothelium12: 41–56.
71.
TahmasebiMPuddefootJRInwangERVinsonGP (1999) The tissue renin–angiotensin system in human pancreas. J Endocrinol161: 317–322.
72.
TalledoOE (1968) Renin–angiotensin system in normal and toxemic pregnancies. IV. Inactivation of angiotensin in toxemic pregnancy. Am J Obstet Gynecol101: 254–256.
73.
UngerT (2003) Blood pressure lowering and renin–angiotensin system blockade. J Hypertens Suppl21(6): 3–7.
74.
ValdesGNevesLAAAntonLCorthornJChaconCGermainAM. (2005) Distribution of angiotensin-(1–7) and ACE2 in human placentas of normal and pathological pregnancies. Placenta27: 200–207.
75.
Vaz-SilvaJCarneiroMMFerreiraMCPinheiroSVSilvaDASilva-FilhoAL. (2009) The vasoactive peptide angiotensin (1–7), its receptor MAS and the angiotensin converting enzyme type 2 are expressed in the human endometrium. Reprod Sci16: 247–256.
76.
VinsonGPSaridoganEPuddefootJRDjahanbakhchO (1997) Tissue renin–angiotensin systems and reproduction. Hum Reprod12: 651–662.
77.
Vrtacnik-BokalEMeden-VrotecHVerdenikI (2006) Uterine arterial blood flow and the substances of ovarian renin–angiotensin system in women with polycystic ovaries undergoing in vitro fertilization. Eur J Obstet Gynecol Reprod Biol124: 77–81.
78.
WantanabeYShibataKKikkawaFKajiyamaHInoKHattoriA. (2003) Adipocyte derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin–angiotensin system. Clin Cancer Res9: 6497–6503.
79.
YagamiHKurauchiOMurataYOkamotoTMizutaniSTomodaY (1994) Expression of angiotensin-converting enzyme in human placenta and its physiologic role in the fetal circulation. Obstet Gynecol84: 453–457.
80.
YoshimuraY (1997) The ovarian renin–angiotensin system in reproductive physiology. Front Neuroendocrinol18: 247–291.
