Prostate hyperplasia in a transgenic mouse with prostate-specific expression of prolactin

被引:86
作者
Kindblom, J
Dillner, K
Sahlin, L
Robertson, F
Ormandy, C
Törnell, J
Wennbo, H
机构
[1] Univ Gothenburg, Dept Physiol, S-40530 Gothenburg, Sweden
[2] Karolinska Inst, Dept Mol Med, S-17177 Stockholm, Sweden
[3] Karolinska Hosp, Dept Woman & Child Hlth, S-17176 Stockholm, Sweden
[4] Garvan Inst Med Res, Canc Res Program, Sydney, NSW 2010, Australia
[5] AstraZeneca R&D, Astrazeneca Transgenic Ctr, S-43183 Molndal, Sweden
[6] AstraZeneca R&D, Integrat Pharmacol, S-43183 Molndal, Sweden
关键词
D O I
10.1210/en.2002-0187
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Prolactin (PRL) is one of several polypeptide factors known to exert trophic effects on the prostate. We have previously reported a dramatic prostate enlargement with concurrent chronic hyperprolactinemia and elevated serum androgen levels in a PRL transgenic mouse (Mt-PRL) with ubiquitous expression of the transgene. To address the role of local PRL action in the prostate, a new transgenic mouse model (Pb-PRL) was generated using the prostate-specific rat probasin (Pb) minimal promoter to drive expression of the rat PRL gene. Pb-PRL transgenic males developed a significant enlargement of both the dorsolateral and ventral prostate lobes evident from 10 wk of age and increasing with age. Expression of the transgene was restricted to the prostate and detected from 4 wk of age. Low levels of transgenic rat PRL were detectable in the serum of adult Pb-PRL animals. Serum androgen levels were normal. The Pb-PRL prostate displayed significant stromal hyperplasia, ductal dilation, and focal areas of epithelial dysplasia. Quantitative analysis of prostatic tissue cellularity demonstrated a marked increase in the stromal to epithelial ratio in all lobes of Mt-PRL and Pb-PRL transgenic prostates compared with controls. Microdissections demonstrated an increased ductal morphogenesis in dorsolateral and ventral prostate lobes of Mt-PRL prostate vs. Pb-PRL and controls. In conclusion, this study indicates the ability of PRL to promote, directly or indirectly, ductal morphogenesis in the developing prostate and further to induce abnormal growth primarily of the stroma in the adult gland in a setting of normal androgen levels.
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页码:2269 / 2278
页数:10
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共 61 条
  • [11] Cunha G R, 1984, Prog Clin Biol Res, V145, P81
  • [12] STROMAL-EPITHELIAL INTERACTIONS AND HETEROGENEITY OF PROLIFERATIVE ACTIVITY WITHIN THE PROSTATE
    CUNHA, GR
    DONJACOUR, AA
    SUGIMURA, Y
    [J]. BIOCHEMISTRY AND CELL BIOLOGY-BIOCHIMIE ET BIOLOGIE CELLULAIRE, 1986, 64 (06): : 608 - 614
  • [13] MORPHOMETRIC QUANTITATION OF STROMA IN HUMAN BENIGN PROSTATIC HYPERPLASIA
    DEERING, RE
    BIGLER, SA
    KING, J
    CHOONGKITTAWORN, M
    ARAMBURU, E
    BRAWER, MK
    [J]. UROLOGY, 1994, 44 (01) : 64 - 70
  • [14] Molecular characterization of prostate hyperplasia in prolactin Transgenic mice by using cDNA representational difference analysis
    Dillner, K
    Kindblom, J
    Flores-Morales, A
    Pang, ST
    Törnell, J
    Wennbo, H
    Norstedt, G
    [J]. PROSTATE, 2002, 52 (02) : 139 - 149
  • [15] Histopathologic characterization of hereditary benign prostatic hyperplasia
    Doehring, CB
    Sanda, MG
    Partin, AW
    Sauvageot, J
    Juo, H
    Beaty, TH
    Epstein, JI
    Hill, G
    Walsh, PC
    [J]. UROLOGY, 1996, 48 (04) : 650 - 653
  • [16] THE EFFECT OF ANDROGEN DEPRIVATION ON BRANCHING MORPHOGENESIS IN THE MOUSE PROSTATE
    DONJACOUR, AA
    CUNHA, GR
    [J]. DEVELOPMENTAL BIOLOGY, 1988, 128 (01) : 1 - 14
  • [17] Characterization of mice deficient in aromatase (ArKO) because of targeted disruption of the cyp19 gene
    Fisher, CR
    Graves, KH
    Parlow, AF
    Simpson, ER
    [J]. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (12) : 6965 - 6970
  • [18] Prolactin: The new biology of an old hormone
    Goffin, V
    Binart, N
    Touraine, P
    Kelly, PA
    [J]. ANNUAL REVIEW OF PHYSIOLOGY, 2002, 64 : 47 - 67
  • [19] THE RAT PROBASIN GENE PROMOTER DIRECTS HORMONALLY AND DEVELOPMENTALLY-REGULATED EXPRESSION OF A HETEROLOGOUS GENE SPECIFICALLY TO THE PROSTATE IN TRANSGENIC MICE
    GREENBERG, NM
    DEMAYO, FJ
    SHEPPARD, PC
    BARRIOS, R
    LEBOVITZ, R
    FINEGOLD, M
    ANGELOPOULOU, R
    DODD, JG
    DUCKWORTH, ML
    ROSEN, JM
    MATUSIK, RJ
    [J]. MOLECULAR ENDOCRINOLOGY, 1994, 8 (02) : 230 - 239
  • [20] MORPHOLOGICAL AND FUNCTIONAL-HETEROGENEITY IN THE RAT PROSTATIC GLAND
    HAYASHI, N
    SUGIMURA, Y
    KAWAMURA, J
    DONJACOUR, AA
    CUNHA, GR
    [J]. BIOLOGY OF REPRODUCTION, 1991, 45 (02) : 308 - 321