Tissue‐specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor‐α knock‐out mice
Open Access
- 18 February 2008
- journal article
- research article
- Published by Wiley in Experimental Physiology
- Vol. 93 (5), 658-664
- https://doi.org/10.1113/expphysiol.2007.041806
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 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.Keywords
This publication has 31 references indexed in Scilit:
- ACE2 and ANG-(1-7) in the rat uterus during early and late gestationAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2008
- Estrogen Protects Against Increased Blood Pressure in Postpubertal Female Growth Restricted OffspringHypertension, 2007
- Temporal-spatial expression of ANG-(1-7) and angiotensin-converting enzyme 2 in the kidney of normal and hypertensive pregnant ratsAmerican Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 2007
- Angiotensin metabolism in renal proximal tubules, urine, and serum of sheep: evidence for ACE2-dependent processing of angiotensin IIAmerican Journal of Physiology-Renal Physiology, 2007
- Modification of the pulmonary renin–angiotensin system and lung structural remodelling in congestive heart failureClinical Science, 2006
- Distinct roles for ANG II and ANG-(1–7) in the regulation of angiotensin-converting enzyme 2 in rat astrocytesAmerican Journal of Physiology-Cell Physiology, 2006
- Angiotensin-Converting Enzyme 2 (ACE2) and ACE Activities Display Tissue-Specific Sensitivity to Undernutrition-Programmed Hypertension in the Adult RatHypertension, 2005
- Mineralocorticoid Receptor Blocker Increases Angiotensin-Converting Enzyme 2 Activity in Congestive Heart Failure PatientsCirculation Research, 2005
- Organ-specific distribution of ACE2 mRNA and correlating peptidase activity in rodentsPeptides, 2005
- ACE2, a new regulator of the renin–angiotensin systemTrends in Endocrinology & Metabolism, 2004