Localized expression of aromatase in human vascular tissues

被引:151
作者
Harada, N [1 ]
Sasano, H
Murakami, H
Ohkuma, T
Nagura, H
Takagi, Y
机构
[1] Fujita Hlth Univ, Sch Med, Dept Biochem, Toyoake, Aichi 4701192, Japan
[2] Tohoku Univ, Sch Med, Dept Pathol, Sendai, Miyagi 980, Japan
[3] Tohoku Univ, Sch Med, Dept Surg, Sendai, Miyagi 980, Japan
关键词
estrogen; aromatase; in situ hybridization; smooth muscle cell;
D O I
10.1161/01.RES.84.11.1285
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
The atheroprotective effects of estrogen are well established and the presence of an estrogen receptor in vascular tissues has recently been reported. Therefore, we investigated the localization of the estrogen-producing enzyme aromatase in vascular tissues to assess the possible contribution of endocrine, paracrine, and autocrine modes of action. Aromatase was found in human vascular smooth muscle cells (SMCs) but not in endothelial cells on in situ hybridization. These observations were further supported by quantitative analysis of aromatase mRNA and the activity in 15 human vascular specimens. Only trace levels of expression we:re detected in the 3 infants examined, whereas 0.0088 to 0.0806 amol/mu g RNA of aromatase mRNA and 12.9 to 122.3 fmol.h(-1).mg(-1) protein of the activity were detected in 12 of the adult individuals. The switching of tissue-specific exon 1 of the human aromatase gene was also observed in some cases. Aromatase was found to be expressed only in cultured SMCs and not in cultured endothelial cells of human aorta and pulmonary artery and to be regulated through dexamethasone and the signaling pathways of protein kinase A and C. Study results revealed the localized expression of aromatase in vascular SMCs, which indicated a possible direct action of locally produced estrogen in an autocrine or paracrine manner, with possible cross talk between smooth muscle and endothelial cells.
引用
收藏
页码:1285 / 1291
页数:7
相关论文
共 47 条
[11]  
FISHERDZOGA K, 1983, EXP MOL PATHOL, V39, P355
[12]   ESTRONE AND ESTRADIOL CONTENT IN HUMAN BREAST TUMORS - RELATIONSHIP TO ESTRADIOL RECEPTORS [J].
FISHMAN, J ;
NISSELBAUM, JS ;
MENENDEZBOTET, CJ ;
SCHWARTZ, MK .
JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY, 1977, 8 (08) :893-896
[13]   EXPERIMENTAL ATHEROSCLEROSIS - EFFECTS OF ESTROGEN AND ATHEROSCLEROSIS ON THROMBOXANE AND PROSTACYCLIN FORMATION [J].
FOGELBERG, M ;
VESTERQVIST, O ;
DICZFALUSY, U ;
HENRIKSSON, P .
EUROPEAN JOURNAL OF CLINICAL INVESTIGATION, 1990, 20 (01) :105-110
[14]   Coronary disease in youth - Comparison of 100 patients under 40 with 300 persons past 80 [J].
Glendy, RE ;
Levine, SA ;
White, PD .
JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION, 1937, 109 :1775-1781
[15]   TAMOXIFEN DECREASES THE RATE OF PROLIFERATION OF RAT VASCULAR SMOOTH-MUSCLE CELLS IN CULTURE BY INDUCING PRODUCTION OF TRANSFORMING GROWTH-FACTOR-BETA [J].
GRAINGER, DJ ;
WEISSBERG, PL ;
METCALFE, JC .
BIOCHEMICAL JOURNAL, 1993, 294 :109-112
[17]   TISSUE-SPECIFIC EXPRESSION OF THE HUMAN AROMATASE CYTOCHROME-P-450 GENE BY ALTERNATIVE USE OF MULTIPLE EXONS-1 AND PROMOTERS, AND SWITCHING OF TISSUE-SPECIFIC EXONS-1 IN CARCINOGENESIS [J].
HARADA, N ;
UTSUMI, T ;
TAKAGI, Y .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1993, 90 (23) :11312-11316
[18]  
HARADA N, 1995, PHARMACOGENETICS, V5, P59
[19]   EFFECTS OF ESTROGEN REPLACEMENT THERAPY ON SERUM-LIPID VALUES AND ANGIOGRAPHICALLY DEFINED CORONARY-ARTERY DISEASE IN POSTMENOPAUSAL WOMEN [J].
HONG, MK ;
ROMM, PA ;
REAGAN, K ;
GREEN, CE ;
RACKLEY, CE .
AMERICAN JOURNAL OF CARDIOLOGY, 1992, 69 (03) :176-178
[20]  
Kaga K, 1996, AM J PATHOL, V149, P45