OVARIAN ORIGIN OF PLASMA AND PERITONEAL-FLUID PRORENIN IN EARLY-PREGNANCY AND IN PATIENTS WITH OVARIAN HYPERSTIMULATION SYNDROME

Prorenin is the major product of renin gene expression in the ovary. P lasma levels of prorenin are elevated in ovarian-stimulated patients a nd during early pregnancy. To further elucidate the source of the elev ated plasma levels of prorenin, we measured prorenin, renin activity, angiotensinogen, and steroid hormone levels in the plasma, luteal flui ds (luteal cysts), ascitic fluid, and in ovarian venous samples collec ted from a patient with severe ovarian hyperstimulation syndrome (OHSS ) and ectopic pregnancy. Prorenin/renin was also measured in plasma an d in peritoneal fluid obtained during therapeutic paracentesis from fo ur patients with OHSS. Several corpora luteal fluids were obtained tha t were rich in estradiol (E(2)) and progesterone (P). Ovarian venous E (2) and P were 20-fold higher than in arterial blood and as high or hi gher 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 E(2). A wide range of prorenin concentrations [1279 +/- 918 SD ng/mL/ hr, n = 6] were found in corpora luteal fluids, but in each the proren in concentration was higher than in plasma (494 ng/mL/hr). Prorenin bu t not renin was higher (+23%) in ovarian venous than arterial blood. P rorenin 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 th e corpora lutea with the highest prorenin concentrations. Renin in lut eal cysts and ascitic fluid constituted 3% and 6% of the total renin ( renin + prorenin), respectively. Total renin was also higher in perito neal fluid (1538 +/- 925 ng/mL/hr) than in plasma (375 +/- 237 ng/mL/h r) of the 4 additional patients with severe OHSS. These findings indic ate that the ovary secretes prorenin during early pregnancy and that i ts secretion is directed preferentially from the luteal cysts into the peritoneal cavity. In light of recent evidence of an effect of proren in on the vascular system, the presence of a huge reservoir of proreni n in the peritoneal cavity of patients with ORSS suggests a potential role for prorenin in the pathogenesis of this syndrome.