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Lynette Kilpatrick1 *, Joni Rutter2 , Constance Brinckerhoff2 , Ismail Kola3 , Lois Salamonsen1 *
Prince Henry's Institute of Medical Research, Clayton, Victoria, Australia 1
Department of Pharmacology and Toxicology, Dartmouth Medical School, Hanover, NH, USA 2
Institute of Reproduction and Development, Clayton, Victoria, Australia 3
Matrix metalloproteinases (MMPs) are critical enzymatic mediators of human endometrial remodeling . MMP1 expression is negatively regulated by several steroid hormone receptors (R). The mechanism for downregulation by androgens (A) requires interaction of AR with Ets transcription factors . The mechanism by which progesterone (P) suppresses MMP1 is not known. Ets proteins are expressed in the human endometrium with cell and cycle-stage specificity . Ets1 and Ets2 are present in stromal cells which also express PR-A and in which MMP1 is downregulated by P. Since there is no evidence that P acts directly on the MMP1 promoter via the PR, we postulated an interaction between Ets and the PR. To address this, Ishikawa cells were transfected with an MMP1 promoter/reporter sequence, cDNA for PR-A and/or Ets1 and treated with or without 10-7M P. MMP1 transcription was determined by luciferase assay. MMP1 was not regulated by P alone, by transfection of PR-A cDNA alone nor in the presence of both P and PR-A. MMP1 was significantly upregulated by transfection with Ets1 alone (3.4 fold, p<0.01); this was not affected by either P or PR-A, but was significantly downregulated in the duel presence of P and PR-A (3.3 fold, p<0.05). These data suggest that P does not directly downregulate MMP1 through interaction between PR-A and the MMP1 promoter but requires the mediation of Ets1. Supported by NH&MRC of Australia (grant 971292). LMK is the recipient of an Australian Postgraduate Award.
 Salamonsen LA. 1998 TEM 9(8):305-309.  Schneikert J. et al. 1996 J Biol Chem 271:23907-23913.  Kilpatrick LM. et al. 1998 Aus Soc Reprod Biol 29:54.
This abstract is being presented on Sunday, August 1 at 8:00 AM to 10:15 AM at CUB 2nd Floor Ballroom.