Work

Tissue-specific regulation of ACE/ACE2 and AT 1 /AT 2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor-α knock-out mice: Oestrogen regulation of ACE/ACE2 and AT1/AT2

Year: 2020

Type: article

Abstract: 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 Ang II and Ang-(1-7). Ang II acts at either the AT1 or the AT2 receptor to mediate opposing actions of vasoconstriction/vasodilation. While it is known that estrogen (E2) acts to down-regulate ACE and the AT1 receptors, its regulation of ACE2 and the AT2 receptor and the involvement of a specific estrogen receptor subtype are unknown. To investigate the role of estrogen receptor-α (ERα) in estrogen’s regulation 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 17-β estradiol (6 µg/day) or placebo for 3 months. ACE,ACE2 and AT1/AT2 receptor mRNAs were measured using reverse transcriptase, real-time polymerase chain reaction (RT/RT-PCR). In the kidney, 17-β estradiol showed 1.7 fold down-regulation of ACE mRNA in AAee mice, with 2.1-fold up-regulation of ACE mRNA in ααee mice. 17-β estradiol showed 1.5 and 1.8 fold down-regulation of ACE2 and AT1 receptor mRNA in AAee mice; this regulation was lost in ααee mice. 17-β estradiol showed marked (81-fold) up-regulation of the AT2 receptor mRNA in AAee mice. In the lung 17-β estradiol 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. There was no significant interaction of estrogen with ER in the lung for ACE, ACE2, and AT2 receptor genes. These studies reveal tissue specific regulation by 17-β estradiol of ACE/ACE2 and AT1/AT2 receptor genes with the ERα receptor primarily responsible for the regulation of kidney ACE2 , AT1 receptor, and AT2 receptor genes.

Source: Carolina Digital Repository (University of North Carolina at Chapel Hill)

DOI: 10.17615/yh9e-6t58

Authors: Gallagher, Patricia, Smithies, Oliver, Maeda, Nobuyo, Brosnihan, K. Bridget, Hodgin, Jeffrey B.

Language: English

Topic: Renin-Angiotensin System Studies

Subfield: Cardiology and Cardiovascular Medicine

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Università degli Studi di Firenze, National Institutes of Health, National Heart, Lung, and Blood Institute

Awards: G9000173334, G9000208912