Prorenin in High Concentrations in Human Ovarian Follicular Fluid

Abstract

Although the kidney is a major source of prorenin, the precursor of renin, there are extrarenal sources for plasma prorenin that have not been identified. The selective increase in plasma prorenin at the time of ovulation suggested that one of these sources might be the ovary. Prorenin was therefore measured in fluid aspirated from 18 ovarian follicles and in plasma collected from three women who were undergoing in vitro fertilization. The follicular fluid contained high concentrations of prorenin that were approximately 12 times higher than plasma prorenin. The prorenin from follicular fluid was immunochemically identical to kidney and plasma prorenin. Thus, the ovary is a likely source for the ovulatory peak of plasma prorenin.

Molecular Biology of Human Renin and Its Gene

“…Most other tissues that have been found to express the renin gene apparently release only prorenin [ 12,14,[20][21][22][23][24][25][26][29][30][31]. These data could imply that the prorenin processing enzyme has a highly restricted tissue distribution; however, the prorenin synthesized by the transfected AtT-20 cells was cleaved to active renin at the natural cleavage site (documented by amino terminal sequencing), and the release of renin was regulated by the same stimulus (cAMP; in this case, 8Br-cAMP) that promotes the release of renal renin [32].…”

“…Whereas most investigators have concluded that there is no conversion of prorenin to renin in the circulation [1,12,14,15], it has been reported that the rat kidney releases a protease that cleaves renin in the circulation [39]. Others have proposed that prorenin might have in vivo activity, for example, through reversible activation or after its uptake by peripheral tissues [ 12,21,40]. To address issues such as these, prorenin was infused into rhesus monkeys over a 40-minute period [41].…”

“…This renin can be stored and released in response to such provocative stimuli as beta-adrenergic activation [18,19]. Elements of the renin angiotensin system are also expressed in extrarenal tissues, and there is growing suspicion that local renin angiotensin systems play important roles [12,[20][21][22][23][24][25][26]. At external sites, prorenin rather than renin is predominately released.…”

Features of the renin-angiotensin system in ascites and pleural effusion during severe ovarian hyperstimulation syndrome

“…Besides, levels of Ang II-ir and of prorenin were comparable in the plasma and in the pleural liquid, while they were clearly higher in the ascites, even though ascites and pleural fluid displayed a similar total protein count. Our present observation provides additional support for the ovarian origin of prorenin and Ang IIir in the ascites of OHSS, given the existence of an ovarian RAS able to produce prorenin locally (9) and Ang II (10) and the stimulatory role of gonadotropins on this local system (11). In patient 2, levels of prorenin and Ang II-ir were slightly higher in the pleural fluid than in the plasma.…”

“…In this regard, the correction of abdominal ascites by a chest tube placed to drain pleural effusion has been reported recently in a patient with severe OHSS (12). Plasma levels of renin activity, active renin, prorenin, and Ang II-ir were clearly higher than those observed in patients stimulated with gonadotropins for IVF on the day of oocyte retrieval (9)(10)(11)13), suggesting peripheral stimulation of the RAS during OHSS. Active renin was measured by an immunoradiometric assay.…”