Immunohistochemical detection of cathepsin D in endometrium from long-term subdermal levonorgestrel users and during the normal menstrual cycle

A previous report has shown that progesterone up-regulates cathepsin D expression in human endometrial cell culture. In women using the levonorgestrel-releasing implant Norplant (R), the plasma levonorgestrel and immunoreactive endometrial progesterone receptor concentrations are elevated. However, the functional status of these receptors is not known. This study used endometrial cathepsin D expression both as an indirect marker for the functional status of endometrial progesterone receptors, and to identify the cell types that express cathepsin D. The results show that cathepsin D is primarily found in glandular epithelia and luminal epithelia in control and Norplant (R) endometria. There is no significant difference in cathepsin D expression between the control and Norplant endometria, between the various stages of the menstrual cycle, or between Norplant users with varying degrees of breakthrough bleeding. Cathepsin D is also detected in cells scattered in the stroma in both control and Norplant endometria. The majority of these cells are macrophages. These data indicate that there is no evidence for progesterone regulation of cathepsin D in the human endometrium. Cathepsin D thus cannot be used as a marker for the functional status of progesterone receptors found in the Norplant-exposed endometrium.