Characterization of the ERbeta-/-mouse heart.
Although the heart responds to estrogen, it is not clear whether estrogen acts directly on heart muscle or indirectly by means of the vascular, immune, or nervous system. No role for estrogen receptor (ER) beta in the heart has been established, but ERbeta(-/-) mice are hypertensive, and as they age, their hearts become enlarged. Histological and ultrastructural analysis of the heart revealed a disarray of myocytes, a disruption of intercalated discs, an increase in the number and size of gap junctions, and a profound alteration in nuclear structure, concomitantly with a loss of expression of lamin A/C from the nuclear envelope. In the lungs of ERbeta(-/-) mice, lamin A/C was located in the nuclear membrane, indicating that lamin A/C is not an ERbeta-regulated gene. Immunohistochemical studies with ERbeta antibodies failed to detect ERbeta in the myocardium. We conclude that abnormalities in heart morphology in ERbeta(-/-) mice are likely due to stress on the nuclear envelope as a result of the chronic sustained systolic and diastolic hypertension observed in ERbeta(-/-) mice. Because neither ERalpha nor ERbeta could be detected in heart muscle, the effects of estrogen on the myocardium seem to be indirect.
Förster
Carola
C
Department of Medical Nutrition, Karolinska Institutet, Novum, S-141 86 Huddinge, Sweden.
Kietz
Silke
S
Hultenby
Kjell
K
Warner
Margaret
M
Gustafsson
Jan-Ake
JA
D000818:Animals; D015153:Blotting, Western; D047629:Estrogen Receptor beta / Q000172:deficiency* / Q000235:genetics / Q000378:metabolism*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D034882:Lamins / Q000096:biosynthesis; D008168:Lung / Q000378:metabolism; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D046529:Microscopy, Electron, Transmission; D008856:Microscopy, Fluorescence; D009206:Myocardium / Q000166:cytology / Q000378:metabolism* / Q000473:pathology / Q000648:ultrastructure; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure; D009685:Nuclear Envelope / Q000378:metabolism / Q000648:ultrastructure
D047629:Estrogen Receptor beta; D034882:Lamins