17 Beta-estradiol regulates the expression of endothelin receptor type B in the heart.
(1) Little is known about the interaction of 17beta-estradiol (E2) and the vasoactive endothelin system in the heart. Endothelin signaling is activated in a failing heart and may contribute to myocardial dysfunction and remodeling. Therefore, we investigated the regulation of proteins of the endothelin system (ppET-1, ECE and ETA-R and ETB-R) in the hearts of female spontaneously hypertensive rats (SHR) with respect to E2. (2) Relative expression levels of the respective cardiac mRNA obtained from sham-operated, ovariectomized and ovariectomized E2-substituted SHR were quantified by real-time PCR. Ovariectomy led to a significant upregulation of the ETB-R mRNA (2.6+/-0.8-fold) in the left ventricular myocardium, which was not attendant with an alteration of ETA-R, ECE and ppET-1 mRNA expression. (3) An upregulation of the relative expression level of ETB-R protein due to ovariectomy was also demonstrated by radioligand binding assay. (4) Upregulation of both ETB-R mRNA and ETB-R protein expression was completely inhibited by E2 replacement. (5) To confirm these results in in vitro experiments, we quantified the mRNA of ET-R subtypes from isolated cardiomyocytes in the presence and absence of E2 (10-8 m, 24 h). Our data showed a markedly downregulated level of ETB-R mRNA in cardiomyocytes stimulated with E2. ETB-R downregulation was not attendant with the alteration of ETA-R, ECE and ppET-1 mRNA expression. (6) Taken together, these data demonstrate that estrogen regulates the expression of ETB-R in rat ventricular myocardium in vivo and in vitro. These observations may help to understand gender-based differences found in cardiovascular disease.
Nuedling
Simone
S
Institut für Physiologie II, Wilhelmstr. 35-37, Universitatsklinikum Bonn 53111, Germany.
van Eickels
Martin
M
Alléra
Axel
A
Doevendans
Pieter
P
Meyer
Rainer
R
Vetter
Hans
H
Grohé
Christian
C
D000818:Animals; D004305:Dose-Response Relationship, Drug; D019332:Endothelin-1 / Q000378:metabolism / Q000494:pharmacology; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects* / Q000502:physiology; D006973:Hypertension / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010052:Ovariectomy; D011485:Protein Binding / Q000187:drug effects / Q000502:physiology; D051381:Rats; D011918:Rats, Inbred SHR; D044023:Receptor, Endothelin B / Q000819:agonists / Q000096:biosynthesis*
D019332:Endothelin-1; D044023:Receptor, Endothelin B; D004958:Estradiol