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 AT₁ 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‐α (ERα) 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 ERα (AAee) or without the ERα (ααee) were treated with 17β‐oestradiol (6 μg 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, 17β‐oestradiol showed 1.7‐fold downregulation of ACE mRNA in AAee mice, with 2.1‐fold upregulation of ACE mRNA in ααee mice. 17β‐Oestradiol showed 1.5‐ and 1.8‐fold downregulation of ACE2 and AT₁ receptor mRNA in AAee mice; this regulation was lost in ααee mice. 17β‐Oestradiol showed marked (81‐fold) upregulation of the AT₂ receptor mRNA in AAee mice. In the lung, 17β‐oestradiol treatment had no effect on AT₁ receptor mRNA in AAee mice, but resulted in a 1.5‐fold decreased regulation of AT₁ mRNA in ααee mice. There was no significant interaction of oestrogen with ERα in the lung for ACE, ACE2 and AT₂ receptor genes. These studies reveal tissue‐specific regulation by 17β‐oestradiol of ACE/ACE2 and AT₁/AT₂ receptor genes, with the ERα receptor being primarily responsible for the regulation of kidney ACE2, AT₁ receptor and AT₂ receptor genes.

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