Tissue‐specific regulation of ACE/ACE2 and AT1/AT2 receptor gene expression by oestrogen in apolipoprotein E/oestrogen receptor‐α knock‐out mice
Key result
17beta-oestradiol demonstrated tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor genes, with ERalpha primarily responsible for regulating kidney ACE2, AT1, and AT2 receptor genes.
Population
Ovariectomized female mice lacking apolipoprotein E with the ERalpha or without the ERalpha
Comparison
17beta-oestradiol (6 microg day(-1)) for 3 months vs Placebo for 3 months
Design
Preclinical
Follow-up
3 months
Authors
Discussion
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Member takes
Implication
Hypothesis-generating for ERalpha-mediated renal RAS modulation; human studies needed before clinical relevance.
Key Points
- To determine how 17beta-oestradiol regulates ACE, ACE2, and angiotensin receptor subtypes in the lung and kidney, and whether this regulation requires oestrogen receptor-alpha.
- Ovariectomized female mice lacking apolipoprotein E with intact (AAee) or deleted (alphaalphaee) oestrogen receptor-alpha received 17beta-oestradiol (6 microg day(-1)) or placebo for 3 months.
- Reverse transcriptase real-time polymerase chain reaction was utilized to quantify mRNA levels of ACE, ACE2, AT1 receptor, and AT2 receptor in renal and pulmonary tissues.
- In the kidney of AAee mice, 17beta-oestradiol caused 1.7-fold downregulation of ACE, 1.5-fold downregulation of ACE2, 1.8-fold downregulation of AT1 receptor, and marked 81-fold upregulation of AT2 receptor mRNA; ACE2 and AT1 regulation ceased in alphaalphaee mice, where ACE mRNA was instead upregulated 2.1-fold.
- In the lung, 17beta-oestradiol induced a 1.5-fold downregulation of AT1 receptor mRNA only in alphaalphaee mice, with no significant interaction between oestrogen and oestrogen receptor-alpha for pulmonary ACE, ACE2, or AT2 receptor expression.
Structured PICO
P
Population
Ovariectomized female mice lacking apolipoprotein E (ee) with the ERalpha (AAee) or without the ERalpha (alphaalphaee)
I
Intervention
17beta-oestradiol (6 microg day(-1)) for 3 months
C
Comparator
Placebo for 3 months
O
Outcome
ACE, ACE2, AT1 receptor and AT2 receptor mRNAs in lung and kidneysurrogate
17beta-oestradiol provides tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor genes, with the ERalpha receptor primarily responsible for regulation in the kidney.
Cite This Study
Brosnihan et al. (2008) studied Regulation of ACE/ACE2 and AT1/AT2 receptor gene expression. 17beta-oestradiol vs. Placebo was evaluated on ACE, ACE2, AT1 receptor and AT2 receptor mRNAs in lung and kidney. 17beta-oestradiol demonstrated tissue-specific regulation of ACE/ACE2 and AT1/AT2 receptor genes, with ERalpha primarily responsible for regulating kidney ACE2, AT1, and AT2 receptor genes.