Uteroglobin: structure, molecular biology, and new perspectives on its function as a phospholipase A2 inhibitor.

UG or blastokinin is a low molecular weight protein which is secreted by the endometrium of the rabbit during early pregnancy. Its synthesis and secretion by the endometrium are regulated by ovarian steroids, especially P. However, the protein is also produced by tracheo-bronchial, gastrointestinal, prostatic, and seminal vesicular epithelium. In the respiratory tract, UG synthesis is under glucocorticoid control. The hormonal regulation of UG synthesis in organs other than the endometrium and tracheobronchial epithelium is poorly understood. The structure of this protein and its gene has been extensively investigated while its physiological function is still unclear. Since UG, after reduction of its two disulfide bonds, has the ability to bind P and related steroids, it has been suggested that this protein is a P carrier or a P scavenger. However, the protein does not bind glucocorticoids, estrogens, or androgens and its presence in organs other than the uterus cannot be explained on the basis of its P binding. Recent data indicate that UG has other interesting biological properties. These include antichemotactic/antiphagocytic effects on macrophages, monocytes, and neutrophils, tolerogenic effect on both blastomeres and spermatozoa against recognition by maternal lymphocytes, and its ability to inhibit thrombin-induced platelet aggregation. Moreover, UG has been shown to be a potent phospholipase A2 inhibitor. The latter property could suggest a possible mechanism of some of the observed biological effects of this protein. The structural similarities of UG with phospholipase A2 and with other PLA2 inhibitory proteins like lipocortins may suggest that the physiological function of this protein may be primarily immunomodulatory through its function as a PLA2 inhibitor. The possible occurrence of similar proteins in other species, including humans, may confirm this hypothesis. Additionally, our hypothesis may lend support to the suggestion that P may be nature's immunosuppressant during pregnancy.