EXPRESSION OF TISSUE INHIBITOR OF METALLOPROTEINASES-1 IN THE HUMAN CORPUS-LUTEUM AFTER LUTEAL RESCUE

Tissue inhibitor of metalloproteinases-1 (TIMP-1) is a specific inhibi tor of a group of proteolytic enzymes known as matrix metalloproteinas es. These enzymes have been widely implicated in the process of tissue remodelling. Extensive remodelling occurs in the corpus luteum during luteolysis unless human chorionic gonadotrophin (hCG) is produced by the early conceptus. This study aimed to investigate the expression an d localisation of TIMP-1 in human corpora lutea during the luteal phas e of the cycle and after luteal rescue with exogenous hCG to mimic the changes of early pregnancy. Human corpora lutea from the early (n=4), mid- (n=4) and late (n=4) luteal phases and after luteal rescue by hC G (n=4) were obtained at the time of hysterectomy. Expression of TIMP- 1 was investigated in these tissues by Western blotting, immunohistoch emistry, Northern blotting and in situ hybridisation. Luteal cells of thecal origin were distinguished from those of granulosa origin by imm unostaining for 17 alpha-hydroxylase. A 30 kDa protein consistent with TIMP-1 was detected in human corpora lutea. This protein was localise d to the granulosa lutein cells in all tissues examined. TIMP-1 mRNA w as found in large quantities in all glands examined and this again loc alised to the granulosa lutein cells. The expression and localisation of TIMP-1 did not change throughout the luteal phase and was not alter ed by luteal rescue. The function of this uniform expression of TIMP-1 in the corpus luteum is not clear but these data suggest that the inh ibition of structural luteolysis during maternal recognition of pregna ncy is not mediated by regulation of TIMP-1 expression.