The Progesterone Receptor Coactivator Hic-5 Is Involved in the Pathophysiology of Endometriosis

被引:69
作者
Aghajanova, Lusine [1 ]
Velarde, Michael C. [1 ]
Giudice, Linda C. [1 ]
机构
[1] Univ Calif San Francisco, Dept Obstet Gynecol & Reprod Sci, San Francisco, CA 94143 USA
基金
美国国家卫生研究院;
关键词
FOCAL ADHESION PROTEIN; STROMAL CELLS; GROWTH-FACTOR; GENE-EXPRESSION; MESSENGER-RNA; WOMEN; DECIDUALIZATION; CALCITONIN; PAXILLIN; DOMAIN;
D O I
10.1210/en.2009-0008
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Endometriosis is an estrogen-dependent disorder primarily associated with pelvic pain and infertility in up to 10% of women of reproductive age. Recent studies suggest that resistance to progesterone action may contribute to the development and pathophysiology of this disorder. In this study we examined the in vivo and in vitro expression and function of one progesterone receptor (PR) coactivator, Hic-5, in human endometrium and endometrial stromal fibroblasts (hESFs) from 29 women with and 30 (control) women without endometriosis. Hic-5 was highly expressed in stromal, but not epithelial, cells in women without endometriosis, in a cycle-dependent manner. In contrast, Hic-5 expression was not regulated during the menstrual cycle in hESFs from women with endometriosis and was significantly reduced in hESFs from women with vs. without disease. Hic-5 mRNA expression throughout the cycle in endometrium from control women, but not those with endometriosis, correlated with expression of PR. Hic-5 mRNA in hESFs was significantly up-regulated in control but not endometriosis hESFs after treatment in vitro with 8-bromoadenosine-cAMP for 96 h but only modestly after 14 d of progesterone treatment. Hic-5 silencing did not influence cAMP-regulated gene expression but affected genes regulated solely by progesterone (e. g. DKK1 and calcitonin). Together the data suggest that the proposed progesterone resistance in endometrium from women with endometriosis derives, in part, from impaired expression of the PR coactivator, Hic-5, in endometrial tissue and cultured endometrial stromal fibroblasts. (Endocrinology 150: 3863-3870, 2009)
引用
收藏
页码:3863 / 3870
页数:8
相关论文
共 41 条
[1]   Steroidogenic Enzyme and Key Decidualization Marker Dysregulation in Endometrial Stromal Cells from Women with Versus Without Endometriosis [J].
Aghajanova, L. ;
Hamilton, A. ;
Kwintkiewicz, J. ;
Vo, K. C. ;
Giudice, L. C. .
BIOLOGY OF REPRODUCTION, 2009, 80 (01) :105-114
[2]  
*AM FERT SOC, 1985, FERTIL STERIL, V43, P351
[3]   Progesterone receptor isoform A but not B is expressed in endometriosis [J].
Attia, GR ;
Zeitoun, K ;
Edwards, D ;
Johns, A ;
Carr, BR ;
Bulun, SE .
JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, 2000, 85 (08) :2897-2902
[4]   Gene induction and categorical reprogramming during in vitro human endometrial fibroblast decidualization [J].
Brar, AK ;
Handwerger, S ;
Kessler, CA ;
Aronow, BJ .
PHYSIOLOGICAL GENOMICS, 2001, 7 (02) :135-148
[5]   Progesterone receptor regulates decidual prolactin expression in differentiating human endometrial stromal cells [J].
Brosens, JJ ;
Hayashi, N ;
White, JO .
ENDOCRINOLOGY, 1999, 140 (10) :4809-4820
[6]   Progesterone resistance in endometriosis: Link to failure to metabolize estradiol [J].
Bulun, SE ;
Cheng, YH ;
Yin, P ;
Imir, G ;
Utsunomiya, H ;
Attar, E ;
Innes, J ;
Kim, JJ .
MOLECULAR AND CELLULAR ENDOCRINOLOGY, 2006, 248 (1-2) :94-103
[7]   Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis [J].
Burney, Richard O. ;
Talbi, Said ;
Hamilton, Amy E. ;
Vo, Kim Chi ;
Nyegaard, Mette ;
Nezhat, Camran R. ;
Lessey, Bruce A. ;
Giudice, Linda C. .
ENDOCRINOLOGY, 2007, 148 (08) :3814-3826
[8]   FOXO1A differentially regulates genes of decidualization [J].
Buzzio, Oscar L. ;
Lu, Zhenxiao ;
Miller, Curt D. ;
Unterman, Terry G. ;
Kim, J. Julie .
ENDOCRINOLOGY, 2006, 147 (08) :3870-3876
[9]  
Christian Mark, 2002, Reprod Biomed Online, V4 Suppl 3, P24
[10]   The focal adhesion protein Hic-5 is highly expressed in the rat myometrium during late pregnancy and labour and co-localizes with FAK [J].
Croke, Jenn M. ;
Pike, Luke R. G. ;
MacPhee, Daniel J. .
REPRODUCTIVE BIOLOGY AND ENDOCRINOLOGY, 2007, 5 (1)