CHANGES IN HEPATIC ANDROGEN SENSITIVITY AND GENE-EXPRESSION DURING AGING

被引：17

作者：

CHATTERJEE, B ^{[1
]}

ROY, AK ^{[1
]}

机构：

[1] UNIV TEXAS,HLTH SCI CTR,DEPT OBSTET & GYNECOL,SAN ANTONIO,TX 78284

来源：

JOURNAL OF STEROID BIOCHEMISTRY AND MOLECULAR BIOLOGY | 1990年 / 37卷 / 03期

关键词：

D O I：

10.1016/0960-0760(90)90495-7

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：

The hepatic tissue of the male rat exhibits a gradual decline and ultimate loss in androgen responiveness during in vivo aging. Appearance of the age-associated androgen insensitivity can be delayed by dietary calorie restriction, an effective means for life-span extension. The androgen receptor mRNA is detectable in the liver only in its androgen-responsive state. Pubertal appearance of hepatic androgen sensitivity is remarkably correlated with the concomitant appearance of a cytoplasmic androgen binding (CAB) protein. Androgen resistance during senescence is associated with the loss of heptic CAB activity as well. We are investigating the molecular basis for the temporal modulation of this hormone sensitivity through studies on the differential expression of two androgen-responsive marker genes. These are the androgen-repressible SMP-2, and the androgen-inducible alpha-2u-globulin. Androgen resistance of hepatocytes during aging results in repression of the alpha-2u-globulin gene, and derepression of the SMP-2 gene. The structural organizations for both of these genes have been characterized. The role of nuclear transcription factors (androgen receptor and any other transacting factor(s) which may be involved) in the coordinate regulation of alpha-2u-globulin and SMP-2 during aging and nutritional manipulation is being explored to establish the molecular mechanism of andropause in the liver.

引用

页码：437 / 445

页数：9

共 22 条

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[2]

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[3]

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[4]

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[5]

Chatterjee, Nath, Roy, Differential regulation of the messenger RNA for three major senescence marker proteins in male rat liver, J. Biol. Chem., 256, pp. 5939-5941, (1981)

[6]

Sarkar, Sarkar, Hunter, Poulik, Roy, Cytoplasmic androgen binding protein of rat liver: molecular characterization after photo-affinity labeling and functional correlation with the age-dependent synthesis of α2u globulin, Biochemistry, 26, pp. 3965-3970, (1987)

[7]

Demyan, Sarkar, Murty, Roy, Purification and immunochemical characterization of the cytoplasmic androgen-binding protein of rat liver, Biochemistry, 28, pp. 1732-1736, (1989)

[8]

Roy, Nath, Motwani, Chatterjee, Age- and androgen-dependent regulation of polymorphic forms of α2u globulin, J. Biol. Chem., 258, pp. 10123-10127, (1983)

[9]

Roy, Chatterjee, Hormonal regulation of hepatic gene expression during aging, Molecular Basis of Aging, pp. 143-165, (1984)

[10]

Motwani, Caron, Demyan, Chatterjee, Poulik, Hunter, Roy, Monoclonal antibody to α2u globulin synthesizing hepatocytes after androgenic induction and aging, J. Biol. Chem., 259, pp. 3653-3657, (1984)

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