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Ovarian Origin of Plasma and Peritoneal Fluid Prorenin in Early Pregnancy and in Patients with Ovarian Hyperstimulation Syndrome¹

Department of Obstetrics and Gynecology (J.I-E., S.K., N.L.), Rambam Medical Center and Technion-Israel Institute of Technology, Faculty of Medicine, Haifa 31096, Israel; Cardiovascular Center (J.E.S.), The New York Hospital—Cornell University Medical College, New York, New York 10021

Address correspondence and reprint requests to: Joseph Itskovitz-Eldor M.D., D.Sc., Department of Obstetrics and Gynecology, Rambam Medical Center, Haifa 31096 Israel.

Prorenin is the major product of renin gene expression in the ovary. Plasma levels of prorenin are elevated in ovarian-stimulated patients and during early pregnancy. To further elucidate the source of the elevated plasma levels of prorenin, we measured prorenin, renin activity, angiotensinogen, and steroid hormone levels in the plasma, luteal fluids (luteal cysts), ascitic fluid, and in ovarian venous samples collected from a patient with severe ovarian hyperstimulation syndrome (OHSS) and ectopic pregnancy. Prorenin/renin was also measured in plasma and in peritoneal fluid obtained during therapeutic paracentesis from four patients with OHSS.

Several corpora luteal fluids were obtained that were rich in estradiol (E₂) and progesterone (P). Ovarian venous E₂ and P were 20-fold higher than in arterial blood and as high or higher than the levels detected in the luteal fluids. The ratios of the hormonal levels in ascitic fluid and plasma were 1.9 for P and 1.4 for E₂. A wide range of prorenin concentrations [1279 ± 918 SD ng/mL/hr, n = 6] were found in corpora luteal fluids, but in each the prorenin concentration was higher than in plasma (494 ng/mL/hr). Prorenin but not renin was higher (+23%) in ovarian venous than arterial blood. Prorenin in the 7 liters of ascitic fluid aspirated (2686 ng/mL/hr) was 5-fold higher than in plasma and similar to the levels measured in the corpora lutea with the highest prorenin concentrations. Renin in luteal cysts and ascitic fluid constituted 3% and 6% of the total renin (renin + prorenin), respectively. Total renin was also higher in peritoneal fluid (1538 ± 925 ng/mL/hr) than in plasma (375 ± 237 ng/mL/hr) of the 4 additional patients with severe OHSS.

These findings indicate that the ovary secretes prorenin during early pregnancy and that its secretion is directed preferentially from the luteal cysts into the peritoneal cavity. In light of recent evidence of an effect of prorenin on the vascular system, the presence of a huge reservoir of prorenin in the peritoneal cavity of patients with OHSS suggests a potential role for prorenin in the pathogenesis of this syndrome.

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