It is known that renin is present in fetal membranes, with the highest concentration in the chorion laeve (reflected chorion). The purpose of this study was to identify and localize renin in human chorion laeve. Indirect immunofluorescent analysis, using antiserum against pure human kidney renin, revealed a single layer of cells in the chorion with strongly positive fluorescence. The presence of atrophic villi in this layer together with other morphological evidence indicate that the cells which are positive for renin are cytotrophoblasts. Isolated cells were prepared from the chorion by collagenase digestion, followed by filtration and density gradient centrifugation on Percoll. The isolated cells also showed a positive reaction with the immunofluorescent technique. Control experiments with nonimmune serum did not show fluorescent cells. Biochemical analysis using RIA of angiotensin I generated from sheep substrate indicated that most of the renin activity in the isolated cells was present as inactive renin (activated by trypsin). The presence of renin in trophoblastic cells may be of significance in local cardiovascular regulation, events associated with parturition, or pathophysiological manifestations of trophoblastic disease.
Porcine relaxin caused a time- and concentration-dependent increase in the release of renin from decidual cells cultured over a 96 h period. The increase in renin release occurred 24-48 h after exposure and was maximal at 48-72 h. Half-maximal stimulation occurred at a relaxin concentration of 5 ng/ml, and maximal stimulation (250-270%) occurred at concentrations greater than or equal to 10 ng/ml. At each time, greater than 95% of the renin released into the medium was in the form of prorenin. The stimulation of renin release was paralleled by a stimulation of cellular renin content and was completely inhibited by cycloheximide, indicating that relaxin also stimulated renin synthesis. Since renin is present in both cytotrophoblast and decidual cells, these results suggest a paracrine and/or autocrine relationship between relaxin- and prorenin-secreting cells.
Human chorio-amnion from term pregnancy was perfused in vitro in a dual perfusion apparatus. Renin released from the fetal membranes was almost entirely in the form of inactive renin (IR) (trypsin-activated). IR was released from both the chorion side and the amnion side. IR introduced on the chorion side of the chorio-amnion did not appear on the amnion side. When cells isolated from term amnion and chorion were grown in tissue culture, IR was released continuously from chorionic cells but not from amnionic cells. The release of IR did not parallel the release of LDH from cultured chorion cells. Exposure to low calcium medium (with or without EGTA) decreased IR release while LDH release increased (or remained constant). Exposure to the calcium ionophore (A 23187) resulted in a marked decrease in IR release. The release of IR from chorionic cells shows some similarities to the release of HCG from trophoblasts. It is expected that IR release from the chorion will show some similarities to R release from the kidney as well as major differences. The function, regulation, and processing of chorionic IR remain to be elucidated.
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