Estrogen regulation of angiotensin-converting enzyme mRNA
Abstract
Abstract—Estrogen replacement therapy is cardioprotective in postmenopausal women; however, the precise molecular mechanisms for this modulation are not fully elucidated. We previously showed that chronic estrogen replacement therapy reduced angiotensin-converting enzyme (ACE) activity in tissue extracts and serum with an associated reduction in plasma angiotensin II. A reverse transcriptase–polymerase chain reaction assay was developed to determine whether estrogen treatment regulates tissue ACE mRNA concentration. Total RNA was isolated from kidney cortex, kidney medulla, lung, and aorta of ovariectomized Sprague-Dawley rats after 21 days of chronic 17β-estradiol replacement therapy (5 mg pellet per rat SC) or placebo. A marked decrease in densitometric intensity ratios of amplified ACE cDNA to elongation factor-1α control cDNA was observed in all tissues from placebo-treated rats compared with the estradiol-treated rats (renal cortex: 0.29±0.04 versus 0.14±0.02; renal medulla: 0.37±0.04 versus 0.24±0.03; lung: 4.49±0.37 versus 2.49±0.59; and aorta: 0.41±0.04 versus 0.29±0.02; all P<0.05). A comparable reduction in ACE activity was detected in tissue extracts from kidney cortex, kidney medulla, and lung of hormone-treated animals. Incubation of purified rat lung ACE with 1 or 10 μmol/L 17β-estradiol had no effect on enzyme activity. These results suggest that estrogen treatment regulates tissue ACE activity by reducing ACE mRNA concentrations. Thus, the beneficial cardiovascular effects of estrogen may be mediated in part by downregulation of ACE with a consequent reduction in the circulating levels of the vasoconstrictor angiotensin II, a decrease in the metabolism of the vasodilator bradykinin, and an increase in the production of the vasorelaxant angiotensin-(1–7).
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Estrogen inhibits ACE expression and activity in rodent models.
“Researchers have reported that both ACE expression and activity are inhibited by estrogen in rodent models [26-29].”
Plasma APP activity forms a continuous distribution in the general population, suggesting it is a complex quantitative trait likely influenced by multiple genetic loci and nongenetic factors.
“Plasma APP activity has been shown to form a continuous distribution in the general population (Cyr et al. 2001), suggesting that plasma APP activity is a complex quantitative trait likely influenced by multiple genetic loci and nongenetic factors (e.g., smoking and hormone replacement therapy [Gallagher et al. 1999]).”
From A variant in XPNPEP2 is associated with angioedema induced by angiotensin I-converting enzyme inhibitors. (2005) · cites this paper as Gallagher et al. 1999
Gallagher et al. is cited for hormone replacement therapy as a possible nongenetic influence on plasma APP activity. The Results section reports that hormone replacement lowered serum ACE activity in rats, but our copy does not address APP activity or establish an effect of hormone replacement on it. The continuous-distribution finding is attributed to Cyr et al., not Gallagher et al. (LLM, conf=0.78)
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- Authors
- Gallagher, P. E., Li, P., Lenhart, J. R., Chappell, M. C., & Brosnihan, K. B.
- Affiliations
- Wake Forest University Health Sciences (US)
- Venue
- Hypertension
- Published
- 1999-01
- Volume
- 33
- Issue
- 1
- Pages
- 323-328
- ISSN
- 0194-911X (ISSN-L)
- 1524-4563
- OpenAlex
- W2167128829
- Cited by
- 290
- References
- 54
- Citations by year
- 2026: 3 · 2025: 6 · 2024: 3 · 2023: 9 · 2022: 8 · 2021: 14 · 2020: 12 · 2019: 14 · 2018: 11 · 2017: 9 · 2016: 7 · 2015: 4 · 2014: 9 · 2013: 9 · 2012: 7
- FWCI
- 8.73
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Hypertension (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association (HL-56973)
- National Institutes of Health (HL‐56973)
- National Heart, Lung, and Blood Institute (R29HL056973, HL56973)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Renin-Angiotensin System Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- estrogen, angiotensin-converting enzyme, estradiol, estrogen replacement therapy, angiotensin II, postmenopausal women, cardioprotection, renal cortex, renal medulla, lung, aorta, angiotensin-(1-7), bradykinin, ovariectomy
- MeSH terms
- Animals, Aorta, Estradiol, Female, Gene Expression Regulation, Humans, Kidney Cortex, Kidney Medulla, Peptidyl-Dipeptidase A, Lung, Muscle, Smooth, Vascular, Ovariectomy, RNA, Messenger, Transcription, Genetic, Estrogen Replacement Therapy, Rats, Sprague-Dawley, Reverse Transcriptase Polymerase Chain Reaction, Rats
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