Tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-alpha knock-out mice

Experimental Physiology
K Bridget BrosnihanPatricia E Gallagher

Abstract

Angiotensin-converting enzyme (ACE) and ACE2 and the AT1 and AT2 receptors are pivotal points of regulation in the renin-angiotensin system. ACE and ACE2 are key enzymes in the formation and degradation of angiotensin II (Ang II) and angiotensin-(1-7)(Ang-(1-7)). Ang II acts at either the AT1 or the AT2 receptor to mediate opposing actions of vasoconstriction or vasodilatation respectively. While it is known that oestrogen acts to downregulate ACE and the AT(1) receptor, its regulation of ACE2 and the AT2 receptor and the involvement of a specific oestrogen receptor subtype are unknown. To investigate the role of oestrogen receptor-alpha (ERalpha) in the regulation by oestrogen of ACE/ACE2 and AT1/AT2 mRNAs in lung and kidney, ovariectomized female mice lacking apolipoprotein E (ee) with the ERalpha (AAee) or without the ERalpha (alphaalphaee) were treated with 17beta-oestradiol (6 microg day(-1)) or placebo for 3 months. ACE, ACE2, AT1 receptor and AT2 receptor mRNAs were measured using reverse transcriptase, real-time polymerase chain reaction. In the kidney, 17beta-oestradiol showed 1.7-fold downregulation of ACE mRNA in AAee mice, with 2.1-fold upregulation of ACE mRNA in alphaalphaee mice. 17beta-Oestradiol showed 1.5- and...Continue Reading

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