33 11 2013 11 Vol.33, No.11 Nov. 2013 doi: 10.7669/j.issn.0253-357X.2013.11.0765 E-mail: [email protected] Reproduction & Contraception ( , - (renin-angiotensin system, RAS) , : ; - - RAS RAS (RAS); : R711.5 1 RAS AngII , Ang-(1-7) AngI , ) 2 AngII ; ACE2-Ang-(1-7)-Mas RAS [2-4] Ang-(1-7), (1-7) , Ang- AT1 AT2 , , AT1 AT2 / , [5 ,6] E-mail: [email protected] Ang AngII AngII (EMs) ; Tel: +86-311-66003768; Fax: +86-311-66002023; ACE2 AngII ACE2 AngII ; : AngI Ang-(1-7), AngI ACE-AngIIAT1/AT2 AngII ACE AngII [1] ( , Ang-(1-7) Mas RAS, [1,7-10] RAS (angiotensin-converting enzyme, ACE) AT2 RAS : 0253-357X(2013)11-0765-05 II(AngII) 2(ACE2) , , ; :A (renin-angiotensin system, (renin) , ; RAS) AT1 , 050000) AT1 Mas , RAS AT1 G , (GPCR) Ang-(1-7) A 765 (aminopeptidase A, APA) (adipocyte- derived leucine aminopeptidase, A-LAP) , APA (Zn) AngII , ; ; , , ; , AngII , A-LAP AngII A-LAP AngII Mas , , , A-LAP AngII APA (renin) 2 , RAS AngII APA , RAS , , ; APA RAS , AngII [11] , AngII AngII [3,11-13] , AngII AngII , , APA , , AngII, AngII [14,15] , , AngII AngII , , [12] Ang 3 , , RAS , , , Ang RAS, , , AT2 , , , , AT1 [16] AT1 AT2 , , ACE2 , , , - [17,18] ACE AT1 AngII ACE ACE-AngII-AT1/AT2 , , RAS ACE [13] Ang-(1-7) , , ACE , , , AT1 , [3] 766 Ang-(1-7) [19] , Ang-(1-7) AT1, Ang-(1-7) , , AngII ACE Ang-(1-7) AT2 , , ; AngII AT1 AngII-ACE , Ang-(1-7)-ACE2 , [11] , ACE AT1 , [20] Ang-(1-7) 4 RAS RAS , ACE AT1 , RAS , , EMs [21] AngII RAS Ang, AT1 RAS , ACE 2350*G 240*T [27] , ACE- [28] EMs , ACE A2350G EMs AT1, RAS AngII , , AT1 , ; Era AT1 AT2 [31,32] AngII , , Ang / , , , , AT2 , , , Ang , , APA , NEP P-LAP AT1 AngII -1 , p21 , , , RAS , AT2 , RAS , 5 RAS , , [6,26-32] 3 APA, NEP P-LAP , AT2 , AT2 / AT2 [25] , AT1 , AT2 AT2 G2 VEGF , , AT1 ; , I [29] Ang [1,8,9] , G3 , AngII , G1 G2 ; G1 (VEGF) (FGF) , G3 ( FIGO ) , (Ang) , A-LAP [30] , [24] [29] , A-LAP , : VEGF 94 , , , A-LAP AngII , AngII , EMs , AngII (HEC-1A)VEGF A-240T [23] , RAS EMs [22] , G , [21] AngII RAS , 767 Hum Reprod, 1997, 12(3):2804-2. [14] Shibata D, Ando H, Iwase A, et al. Distribution of adipocyte[1] Paul M, Poyan Mehr A, Kreutz R, et al. Physiology of local derived leucine aminopeptidase (A-LAP)/ER-aminopepti- renin-angiotensin systems. Physiol Rev, 2006, 86(3):747- dase (ERAP)-1 in human uterine endometrium. J Histochem 803. Cytochem, 2004, 52(9):1169-75. [2] Johnson IR. Renin substrate, active and acid-activatable renin [15] Ando H, Nagasaka T, Nomura M, et al. Premenstrual disap- concentrations in human plasma and endometrium during pearance of aminopeptidase A in endometrial stromal cells the normal menstrual cycle. Br J Obstet Gynaecol, 1980, 87 around endometrial spiral arteries/arterioles during the de- (10):875-82. cidual change. J Clin Endocrinol Metab, 2002, 87(5):2303-9. [3] Vaz-Silva J, Carneiro MM, Ferreira MC, et al. The vasoactive [16] Schrier RW, Ohara M. Dilemmas in human and rat pregnancy: peptide angiotensin-(1-7), its receptor Mas and the angio- proposed mechanisms relating to arterial vasodilation. J tensin-converting enzyme type 2 are expressed in the human Neuroendocrinol, 2010, 22(5):400-6. endometrium. Reprod Sci, 2009, 16(3):247-56. , [4] , . 2(ACE2)- (Ang)-(1-7)-MAS . , 2011, 31(10):691-4. [17]Brosnihan KB, Bharadwaj MS, Yamaleyeva LM, et al. Decidualized pseudopregnant rat uterus shows marked reduction in Ang II and Ang-(1-7) levels. Placenta, 2012, 33(1): 17-23. [5] Mala C, John AD, Vesta SL, et al. Variationin the rennin [18] Valdes G, Corthorn J, Bharadwaj MS. Utero-placental expres- angiotensin system throughout the normal menstrual cycle. sion of angiotensin-(1-7) and ACE2 in the pregnant guinea- J Am Soc Nephrol, 2002, 13(2):446-52. pig. Reprod Biol Endocrinol, 2013, 11(1):5. [6] Shibata K, Klikkawa F, Mizokami Y, et al. Possible involve- [19] Joyner J, Neves LA, Granger JP, et al. Temporal-spatial ment of adipocyte-derived leucine aminopeptidase via an- expression of ANG-(1-7) and angiotensin-converting enzyme in endometrial carcinoma. Tumour Biol, 2005, 26 2 in the kidney of normal and hypertensive pregnant rats. giotensin (1):9-16. [7] Keidar S, Kaplan M, Gamliel-Lazarovich A. ACE2 of the heart: from angiotensin I to angiotensin (1-7). Cardiovasc Res, 2007, 73(3):463-9. [8] Wright JW, Yamamoto BJ, Harding JW. Angiotensin Am J Physiol Regul Integr Comp Physiol, 2007, 293(1): R169-77. [20] Neves LA, Stovall K, Joyner J, et al. ACE2 and ANG-(1-7) in the ratuterus during early and late gestation.Am J Physiol Regul Integr Comp Physiol, 2008, 294(1):R151-6. receptorsubtype mediated physiologies and behaviors new [21] Abraham F, Sacerdoti F, De Len R, et al. Angiotensin II activates discoveriesand clinical targets. Prog Neurobiol, 2008, 84 (2): the calcineurin/NFAT signaling pathway and induces 157-81. cyclooxygenase-2 expression in rat endometrial stromal cells. [9] Vongpatanasin W, Thomas GD, Schwartz R, et al. Creactive Rev Assoc Med Bras, 2012, 58(5):620-32. protein causes downregulation of vascular angiotensin sub- [22] Hsieh YY, Chang CC, Tsai FJ, et al. Angiotensin I-converting type receptors and systolic hypertension in mice. Circulation, enzyme ACE 2350*G and ACE-240*T-related genotypes 2007, 115(8):1020-8. and alleles are associated with higher susceptibility to [10] Alenina N, Xu P, Rentzsch B, et al. Genetically altered animal models for Mas and angiotensin-(1-7). Exp Physiol, 2008, 93(5):528-37. endometriosis. Mol Hum Reprod, 2005, 11(1):1-4. [23] Hsieh YY, Chang CC, Chen SY, et al. XRCC1 399 Arg-related genotype and allele, but not XRCC1 His107Arg, XRCC1 [11] Ahmed A, Li XF, Shams M, et al. Localization of the Trp194Arg, KCNQ2, AT1R, and hOGG1 polymorphisms, angiotensin II and its receptor subtype expression in human are associated with higher susceptibility of endometriosis. endometrium and identification of a novel high-affinity an- Gynecol Endocrinol, 2012, 28(4):305-9. giotensin II binding site. J Clin Invest, 1995, 96(3):848-57. [24] Touyz RM. Molecular and cellular mechanisms in vascular [12] Li XF, Ahmed A. Dual role of angiotensin II in the human injury in hypertension: role of angiotensin II. Curr Opin endometrium. Hum Reprod, 1996, 11(Suppl 2):95-108. Nephrol Hypertens, 2005, 14(2):125-31. [13] Li XF, Ahmed A. Compartmentalization and cyclic variation [25] Li XF, Ahmed A. Expression of angiotensin II and its receptor of immunoreactivity of renin and angiotensin converting en- subtypes in endometrial hyperplasia: a possible role in dys- zyme in human endometrium throughout the menstrual cycle. functional menstruation. Lab Invest, 1996, 75(2):137-45. 768 [26] Kinoshita J, Fushida S, Harada S, et al. Local angiotensin II- (1):9-16. generation in human gastric cancer: correlation with tumor [30] Piastowska-Ciesielska AW, Puciennik E, Wojcik-Krowiranda progression through the activation of ERK1/2, NF-kappaB K, et al. Analysis of the expression of angiotensin II type 1 and survivin. Int J Oncol, 2009, 34(6):1573-82. receptor and VEGF in endometrial adenocarcinoma with dif- [27] Ino K, Shibata K, Yamamoto E, et al. Role of the reninangiotensin system in gynecologic cancers. Curr Cancer Drug ferent clinicopathological characteristics. Tumour Biol, 2012, 33(3):767-74. [31] Kikkawa F, MizunoM, Shibata K, et al. Activation of inva- Targets, 2011, 11(4):405-11. [28] Watanabe Y, Shibata K, Kikkawa F, et al. Adipocyte-derived leucine aminopeptidase suppresses angiogenesis in human endometrial carcinoma via renin-angiotensin system. Clin Cancer Res, 2003, 9(17):6497-503. [29] Shibata K, Kikkawa F, Mizokami Y, et al. Possible involvement of adipocyte-derived leucine aminopeptidase via an- siveness of cervical carcinoma cells by angiotensin . Am J Obstet Gynecol, 2004, 190(5):1258-63. [32] Ino K, Shibata K, Kajiyama H, et al. Angiotensin II type 1 receptor expression in ovarian cancer and its correlation with tumour angiogenesis and patient survival. Br J Cancer, 2006, 94(4):552-60. giotensin II in endometrial carcinoma. Tumour Biol, 2005, 26 (2013 4 22 ) Local Renin-angiotensin System in Endometrium Yu-mei MA, Wei JIANG, Jie-ying ZHANG (Department of Pathology, the Second Hospital of Hebei Medical University, Shijiazhuang, 050000) ABSTRACT Renin-angiotensin system (RAS) is an important humoral regulation system in human body, the disorder of this system could induce many diseases. Many previous studies focus on this circulating RAS system, local RAS becomes a research hotspot these years. Related studies have shown that local RAS participates in a series of physiological processes such as endometrial periodic changes, reproductive function regulation, and pregnant uterine body homeostasis. And local RAS also participates in the pathological process such as endometriosis (EMs), functional endometrial bleeding and endometrial cancer. Key words: renin-angiotensin system (RAS); angiotensin; angiotensin receptor; endometrium ****************************************************************************************************************************************** 769