STROMAL-EPITHELIAL INTERACTION MEDIATES STEROIDAL REGULATION OF METALLOPROTEINASE EXPRESSION IN HUMAN ENDOMETRIUM

被引:177
作者
OSTEEN, KG
RODGERS, WH
GAIRE, M
HARGROVE, JT
GORSTEIN, F
MATRISIAN, LM
机构
[1] VANDERBILT UNIV,SCH MED,DEPT PATHOL,NASHVILLE,TN 37232
[2] VANDERBILT UNIV,SCH MED,DEPT CELL BIOL,NASHVILLE,TN 37232
[3] UNIV ALABAMA,DEPT PATHOL & OBSTET & GYNECOL,BIRMINGHAM,AL 35233
关键词
CELL-CELL INTERACTIONS; MATRILYSIN; STROMELYSIN; PROGESTERONE; ESTROGEN;
D O I
10.1073/pnas.91.21.10129
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
The hallmark of the menstrual cycle is extensive steroid-dependent tissue turnover. Estrogen mediates endometrial cell growth and structural remodeling, whereas progesterone suppresses estrogen-dependent proliferation and promotes cellular differentiation. In nonfertile cycles, tissue degradation and menstruation occur as a consequence of steroidal deprivation as the ovarian corpus luteum fails. Stromal-epithelial interactions are recognized as a necessary component in mediating steroid-induced endometrial turnover. Specific mRNAs for metalloproteinases of the stromelysin family are expressed during endometrial growth and menstrual breakdown but are absent in the progestin-dominated secretory phase. This expression pattern suggests involvement of stromelysins in remodeling the extracellular matrix of the endometrium during tissue growth and breakdown and implicates progesterone in the suppression of these enzymes. We examined the regulation of endometrial stromelysins in explant cultures and found no acute effect of estradiol on their expression, whereas progesterone was a potent inhibitor of stromelysin expression. Progesterone also suppressed stromelysin expression in cultures of isolated stromal cells, but epithelial cells were progesterone insensitive. Coculture of recombined stromal and epithelial cells restored steroidal suppression of the epithelial-specific metalloproteinase. Our data confirm that progesterone inhibits endometrial stromelysins and further demonstrate the necessity for a stromal-derived factor(s) as a mediator of steroid suppression of an epithelial metalloproteinase.
引用
收藏
页码:10129 / 10133
页数:5
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