THE EFFECT OF LUTEAL RESCUE ON THE EXPRESSION AND LOCALIZATION OF MATRIX METALLOPROTEINASES AND THEIR TISSUE INHIBITORS IN THE HUMAN CORPUS-LUTEUM

Luteolysis is associated with tissue remodeling probably involving the matrix metalloproteinases (MMPs) and their specific tissue inhibitors (TIMPs). This study investigated the expression and localization of t he major MMPs and TIMPs in the human corpus luteum throughout the lute al phase and after luteal rescue with hCG. Corpora lutea (n = 9) were collected at hysterectomy and were dated by serial urinary LH estimati on. In addition, corpora lutea (n = 3) were collected from women who h ad received daily doubling doses of hCG to mimic the hormonal changes of early pregnancy. MMP-1, MMP-2, MMP-9, TIMP-1, TIMP-2, and TIMP-3 we re investigated by zymography, reverse zymography, Northern blotting, and in situ hybridization. There was no change in the expression of MM P-1, TIMP-1, and TIMP-2 throughout the luteal phase or after luteal re scue. Little TIMP-3 could be detected in the corpus luteum. MMP-9 acti vity peaked in the early and late luteal phase. The expression and act ivity of MMP-2 were maximal in the late luteal phase. Exposure to hCG during luteal rescue in, vivo was associated with a reduction (P < 0.0 5) in the expression and activity of MMP-2. Messenger ribonucleic acid s (mRNAs) for MMP-1, MMP-2, and TIMP-2 were localized to the connectiv e tissue stroma and the thecal-lutein cells of the corpus luteum. In c ontrast, TIMP-1 mRNA was localized to the granulosa-lutein cells, and MMP-9 mRNA was expressed in scattered cells within the steroidogenic a nd nonsteroidogenic cell layers. In conclusion, during maternal recogn ition of pregnancy, hCG prevents the normal increase in MMP-2 in the l ate luteal phase. MMPs can function in an environment containing large amounts of TIMP-1, as they have a different cellular localization.