Sequence analysis of a
cDNA clone for the
progesterone-dependent
protein (PDP) of the cat uterus revealed that PDP may be
cathepsin L. This study was undertaken to directly measure the
cathepsin L activity in uterine
flushings from pregnant and ovariectomized
steroid-treated animals in order to confirm that PDP is
cathepsin L. Optimum activity toward the substrate
Z-Phe-Arg-NMec was observed at a pH of 5-6.
Z-Phe-Phe-CHN2, a specific inhibitor of
cathepsin L, significantly inhibited the proteolytic activity present in uterine
flushings. Immunoabsorption of PDP from uterine
flushings obtained from
progesterone (P)-treated cats reduced
cathepsin L proteolytic activity to levels observed in ovariectomized and
estradiol (E2)-treated animals. In E2-primed and E2 + P-treated animals, proteolytic activity in uterine
flushings was detectable after 7 days and peaked after 11-13 days of E2 + P treatment. This proteolytic activity was also dramatically increased before implantation (10-12 days after coitus) in pregnant cats. Thus, our data indicate that changes in
cathepsin L activity in uterine
flushings are correlated with changes in PDP, the uterine
protein synthesized and released from the epithelial cells of the deep uterine glands. PDP, via its
cathepsin L proteolytic activity, may play a role in the implantation process.