VECTORIAL SECRETION OF PROSTAGLANDINS BY POLARIZED RODENT UTERINE EPITHELIAL-CELLS

Uterine epithelial cells (UEC) isolated from mature mice as well as immature mice and rats were cultured on EHS matrix-coated nitrocellulose filters in order to determine their ability to secrete prostaglandin (PG) F2αand PGE2in a polarized manner. Ultrastructural analyses were performed to validate the polar nature of mouse UEC and demonstrate the presence of separate apical and basolateral plasma membrane domains. These properties included the presence of tightly juxtaposed lateral membranes, apical microvilli, and a relatively flat basal surface. Biochemical indices of polarity included the preferential (~5:1) basal uptake of [35S]methionine as well as a preferential (~9:1) apical secretion of protein. UEC isolated from mice during the estrous and diestrous stages of the estrous cycle did not differ in their degree of polarity, as measured by these morphological and biochemical indices. UEC of estrous and diestrous mice as well as immature mice and rats preferentially secreted PGF2αto the basal medium to an approximately 4-fold greater extent than to the apical medium. PGE2was secreted at least 10-fold less than PGF2α, and a preferential basal secretion could not be demonstrated. Polarized UEC accumulated relatively large cellular pools of PGF2α, while nonpolarized cells grown on matrix-coated plastic did not. This difference was reflected by the inability of an inhibitor of PG biosynthesis, indomethacin, to inhibit PGF2αsecretion by polarized cells during short (4-h) incubations. In contrast, this drug effectively inhibited secretion in nonpolarized cells or polarized cells incubated with indomethacin for longer (24-h) intervals. Therefore, cellular PGF2αpools apparently support continued secretion of this lipid even when de novo synthesis is transiently inhibited. Preferential basal secretion of PGF2αwas due to the polar nature of UEC, since disruption of tight junctions with EGTA modified the basal to apical ratio of PGF2αsecretion to near unity. Sodium azide inhibited the secretion of PGF2α, indicating that PGF2αsecretion was energy dependent. PGF2αsecretion was not coupled to protein synthesis or secretion, since cycloheximide did not inhibit this process in polarized or nonpolarized cells. These studies describe the first evidence for polarized secretion of lipid-derived hormones by epithelial cells. The preferential basal secretion of PGF2αmay play an important role in regulating UEC interactions with the underlying stroma. © 1990 by The Endocrine Society.