Differential effects of estrogen and progesterone on AT(1) receptor gene expression in vascular smooth muscle cells

G Nickenig ¹, K Strehlow , S Wassmann

⁰Klinik III für Innere Medizin, Universität zu Köln, Cologne, Germany. georg.nickenig@uni-koeln.de

Circulation +

|

October 12, 2000

View abstract on PubMed

Summary

Estrogen and progesterone have opposing effects on the angiotensin II AT(1) receptor in vascular cells. Estrogen decreases AT(1) receptor expression, while progesterone increases it, impacting cardiovascular disease risk.

Area Of Science

Endocrinology
Cardiovascular Biology
Molecular Biology

Background

Postmenopausal estrogen therapy's vasoprotective effects may be hindered by progestins.
Investigated differential effects of estrogens and progesterone on AT(1) receptor gene expression in vascular smooth muscle cells (VSMCs).

Purpose Of The Study

To elucidate the distinct impacts of estrogen and progesterone on AT(1) receptor expression in VSMCs.
To understand the molecular mechanisms underlying these differential effects.

Main Methods

Northern analysis and Western blotting to assess AT(1) receptor mRNA and protein levels.
Nuclear run-on assays to determine transcription rates.
mRNA half-life studies.
Pharmacological inhibition of signaling pathways (e.g., nitric oxide, PI(3)-kinase).

Main Results

17beta-estradiol downregulated AT(1) receptor mRNA and protein.
Progesterone significantly upregulated AT(1) receptor mRNA and protein.
Estrogen's effect involved estrogen receptors and nitric oxide pathways.
Progesterone's effect involved PI(3)-kinase activation and enhanced mRNA transcription and stability.
Estrogen inhibited reactive oxygen species production; progesterone enhanced it.

Conclusions

Differential regulation of AT(1) receptor by estrogen and progesterone influences cardiovascular disease pathogenesis.
These opposing hormonal effects may explain counteracting impacts on postmenopausal cardiovascular disease incidence.

Related Concept Videos