Progesterone-dependent cathepsin L proteolytic activity in cat uterine flushings.
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.
Li
W G
WG
Department of Obstetrics and Gynecology, University of Illinois College of Medicine of Chicago, Illinois 60680.
Jaffe
R C
RC
Fazleabas
A T
AT
Verhage
H G
HG
D000818:Animals; D056668:Cathepsin L; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D002415:Cats; D003546:Cysteine Endopeptidases; D010450:Endopeptidases; D004958:Estradiol / Q000494:pharmacology; D005260:Female; D006863:Hydrogen-Ion Concentration; D010052:Ovariectomy; D011247:Pregnancy; D011374:Progesterone / Q000494:pharmacology; D014599:Uterus / Q000187:drug effects / Q000201:enzymology*
D011374:Progesterone; D004958:Estradiol; D002403:Cathepsins; D010450:Endopeptidases; D003546:Cysteine Endopeptidases; D056668:Cathepsin L