抄録
Estrogen(E2) regulates the components of the renin-angiotensin system(RAS). Regulation of angiotensinogen (ATG) gene expression by estrogen is well known, however, the effects of estrogen on angiotensin converting enzyme (ACE) remains unclear.
Methods: (Study 1); Thirty female spontaneously hypertensive rats (SHR) at the age of 14 weeks were divided into 3 groups. C group: control group, OVX group: ovariectomy group, OVE group: ovariectomy group with supplementation of E2 (transplant of a 1.5 mg/pellet/90 days sabcutaneously). Systolic blood pressure was measured every 2 weeks until the end of the experiment (22 weeks of age). At the end of the experiment, blood was taken for measurements of angiotensin I (AngI), angiotensin II (AngII), plasma renin activity (PRA), angiotensin converting enzyme (ACE) activity and 17 beta estradiol (E2). Expression of mRNA of ACE in the kidney was examined by using RNase protection assay (RPA). (Study 2); Incubation with E2 (10－9, 10－8, 10－7 M) or Ang II (10－8, 10－7, 10－6 M) in human umbilical vein endothelial cell (HUVEC) was carried out, and expression of ACE mRNA in HUVEC was measured by RPA method. In addition, incubation with both E2(10－7 M) and tamoxifen (10－6 M) in HUVEC was carried out, and expression of ACE mRNA in HUVEC was measured in a similar way.
Results: (Study 1); In rats in the OVX group, Ang II and ACE activity were increased
significantly compared to those in the C group. In contrast, in rats in the OVE group, Ang II and ACE activity were decreased significantly compared to those in the OVX group. Expression of ACE mRNA in kidneys was increased in the OVX group, and was reduced in OVE group. (Study 2); In HUVEC treated with E2, expression of ACE mRNA was decreased dose-dependently and maximally suppressed at 12 h. In HUVEC treated with E2, the suppression of the expression of ACE mRNA was completely protected by the combined administration of Tamoxifen. In HUVEC treated with Ang II, expression of ACE mRNA was increased dose-dependently and maximally increased at 3 h.
Conclusion: E2 suppresses expression of ACE mRNA, and inhibits ACE activity in vivo and in vitro. In contract, AngII promotes production of ACE in vitro. We conclude that E2 is an important regulator of ACE mRNA expression, resulting in the role of the master of the renin-angiotensin system in women.
