Expression of apolipoprotein J in the uterus is associated with tissue remodeling

The endometrium is a dynamic tissue that, in response to hormonal cues, undergoes cycles of growth and involution. Extracellular factors required for this remodeling are poorly understood. The potential role in endometrial turnover of apolipoprotein J (apoJ), a secretory glycoprotein that can bind lipids and membrane-active proteins, is proposed on the basis of its spatial and temporal patterns of expression during normal cycling, after ovariectomy, and in response to hormone manipulation. In the mouse, apoJ mRNA was expressed in uterine luminal and glandular epithelial cells coincident with the presence of apoJ protein. The apoJ gene was differentially expressed in the glandular and uterine luminal epithelial cells during the estrous cycle and following hormone depletion. Expression of apoJ was not induced in ovariectomized mice by estrogen, progesterone, or dexamethasone treatment alone. Progesterone administration after an initial estrogen pretreatment, however, resulted in dramatic induction of apoJ as the progesterone level declined. In contrast, apoJ was not induced when a long-lived progesterone analog, medroxyprogesterone, was substituted for progesterone. In the human menstrual cycle, apoJ was present in glandular lumens only during the late secretory phase. Declining progesterone levels, causing substantial tissue reorganization, are characteristic of the times of marked apoJ induction in uterine epithelial cells. These expression patterns are consistent with apoJ functioning as an extracellular cytoprotectant by mediating clearance of and/or neutralizing cytolytic tissue debris.