ANDROGEN RECEPTORS, 5-ALPHA-REDUCTASE ACTIVITY AND ANDROGEN-DEPENDENT PROLIFERATION OF VASCULAR SMOOTH-MUSCLE CELLS

被引:110
作者
FUJIMOTO, R
MORIMOTO, I
MORITA, E
SUGIMOTO, H
ITO, Y
ETO, S
机构
[1] UNIV OCCUPAT & ENVIRONM HLTH, DEPT MED HUMANITIES, YAHATANISHI KU, KITAKYUSHU, FUKUOKA 807, JAPAN
[2] SUGIMOTO CLIN, KOKURANIMAMI KU, KITAKYUSHU, FUKUOKA 80002, JAPAN
关键词
D O I
10.1016/0960-0760(94)90025-6
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (K-d 7.37 nM, B-max 10.59 fmol/mg protein) and dihydrotestosterone (DHT; K-d 4.89 nM, B-max 11.37 fmol/mg protein) in VSMC. Measurement of Scr-reductase activity suggested that testosterone is converted to DHT in VSMC (K-m 0.36 mu M, V-max 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.
引用
收藏
页码:169 / 174
页数:6
相关论文
共 24 条
[1]   STRUCTURAL-ANALYSIS OF COMPLEMENTARY-DNA AND AMINO-ACID SEQUENCES OF HUMAN AND RAT ANDROGEN RECEPTORS [J].
CHANG, CS ;
KOKONTIS, J ;
LIAO, SS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1988, 85 (19) :7211-7215
[2]  
CHOMCZYNSKI P, 1987, ANAL BIOCHEM, V162, P156, DOI 10.1016/0003-2697(87)90021-2
[3]   A POSSIBLE MECHANISM IN ARTERIAL-WALL FOR MEDIATION OF SEX DIFFERENCE IN ATHEROSCLEROSIS [J].
FISCHER, GM ;
BASHEY, RI ;
ROSENBAUM, H ;
LYTTLE, CR .
EXPERIMENTAL AND MOLECULAR PATHOLOGY, 1985, 43 (03) :288-296
[4]   UP-REGULATION OF THE LEVELS OF ANDROGEN RECEPTOR AND ITS MESSENGER-RNA BY ANDROGENS IN SMOOTH-MUSCLE CELLS FROM RAT PENIS [J].
GONZALEZCADAVID, NF ;
VERNET, D ;
NAVARRO, AF ;
RODRIGUEZ, JA ;
SWERDLOFF, RS ;
RAJFER, J .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 1993, 90 (02) :219-229
[5]   EXPRESSION OF THE ANDROGEN RECEPTOR GENE IN RAT PENILE TISSUE AND CELLS DURING SEXUAL-MATURATION [J].
GONZALEZCADAVID, NF ;
SWERDLOFF, RS ;
LEMMI, CAE ;
RAJFER, J .
ENDOCRINOLOGY, 1991, 129 (03) :1671-1678
[6]   HIGH-DENSITY-LIPOPROTEIN RESPONSE TO 5-ALPHA-DIHYDROTESTOSTERONE AND TESTOSTERONE IN MACACA-FASCICULARIS - A HORMONE-RESPONSIVE PRIMATE MODEL FOR THE STUDY OF ATHEROSCLEROSIS [J].
GREGER, NG ;
INSULL, W ;
PROBSTFIELD, JL ;
KEENAN, BS .
METABOLISM-CLINICAL AND EXPERIMENTAL, 1990, 39 (09) :919-924
[7]   STUDIES ON PATHOGENESIS OF INCOMPLETE FORMS OF ANDROGEN RESISTANCE IN MAN [J].
GRIFFIN, JE ;
WILSON, JD .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 1977, 45 (06) :1137-1143
[8]   TESTOSTERONE AT HIGH-CONCENTRATIONS INTERACTS WITH THE HUMAN ANDROGEN RECEPTOR SIMILARLY TO DIHYDROTESTOSTERONE [J].
GRINO, PB ;
GRIFFIN, JE ;
WILSON, JD .
ENDOCRINOLOGY, 1990, 126 (02) :1165-1172
[9]   INFLUENCE OF SEVERAL C-19 STEROIDS ON THE GROWTH OF INDIVIDUAL MUSCLES OF THE GUINEA PIG [J].
KOCHAKIAN, CD ;
TILLOTSON, C .
ENDOCRINOLOGY, 1957, 60 (05) :607-618
[10]  
McGill H.C., 1979, ATHER REV, V4, P157