Modulation of hypertensive heart disease by estrogen.
Left ventricular hypertrophy is an independent risk factor for morbidity and mortality in patients with hypertensive heart disease. Cardiac hypertrophy, associated with increased cardiac fibrosis and myocardial relaxation impairment, shows gender-based differences with significantly higher mortality in men. The role of estrogen in the pathogenesis of this process is poorly understood. After our previous demonstration that cardiac myocytes and fibroblasts contain functional estrogen receptors, we therefore investigated: 1) the influence of different estrogen metabolites on cardiac fibroblast growth; 2) the influence of different estrogen metabolites on the expression of the immediate early gene c-Fos; 3) the influence of estrogen on the L-type calcium channel in cardiomyocytes.


METHODS
1) Neonatal rat cardiac fibroblasts were incubated with 17 beta-estradiol, estrone, 2-hydroxyestrone, and 2-methoxyestradiol (all 10(-9) M). Bromodeoxyuridine incorporation was measured after 24 h. 2) c-Fos expression was demonstrated by immunoblotting. 3) L-type (Ca2+) current with and without 17 beta-estradiol was assessed in adult guinea pig cardiomyocytes by whole cell patch clamp.


RESULTS
Cardiac fibroblast growth was stimulated by estrogen metabolites with 2-hydroxyestrone as the most potent activator; in addition, 10(-5) M 17 beta-estradiol reduced the L-type Ca2+ current by about 20% in cardiomyocytes.


CONCLUSIONS
Estrogen induces both short term effects (non-genomic) and long term effects (genomic) on the heart and may therefore account for gender- and age-based differences in hypertensive heart disease.
Grohé
C
C
Medizinische Universitäts-Poliklinik, University of Bonn, Germany.
Kahlert
S
S
Löbbert
K
K
Meyer
R
R
Linz
K W
KW
Karas
R H
RH
Vetter
H
H
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004958:Estradiol / Q000494:pharmacology; D004967:Estrogens / Q000378:metabolism* / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects; D005355:Fibrosis / Q000188:drug therapy; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects; D006331:Heart Diseases / Q000150:complications / Q000473:pathology; D006973:Hypertension / Q000150:complications* / Q000188:drug therapy; D009206:Myocardium / Q000166:cytology / Q000378:metabolism / Q000473:pathology*; D018408:Patch-Clamp Techniques; D051381:Rats
D004967:Estrogens; D004958:Estradiol; D002118:Calcium