Prorenin and renin as separate mediators of tissue and circulating systems

The renin gene is expressed in extrarenal tissues. High concentrations of renin occur in female reproductive organs: the adrenals of rats and mice have intermediate levels. The testis also synthesizes renin, as does the anterior pituitary. In contrast, very low levels of renin (ie, below plasma levels) are found in the heart and extrarenal vascular tissues. The predominant form of renin in the human ovary, placenta, and uterus is prorenin and the human ovary, testis, and adrenals have been shown to secrete prorenin into the circulation. The kidney is the only organ that secretes active renin and it is also the major source of plasma prorenin. We have used the ovary as a model to study extrarenal renin. Ovarian prorenin secretion changes dynamically during the menstrual cycle and during gestation. Secretion occurs during the LH surge and when hCG is present in the blood during pregnancy. Plasma active renin does not change concurrently and only low levels of active renin are found in association with very high concentrations of prorenin in ovarian follicular fluid after gonadotropin stimulation. To explain the preponderance of prorenin, and the virtual absence of renin in the ovary we hypothesize that prorenin need not be converted to active renin to have effect. In vitro, when prorenin is acidified to pH 3.3 or cooled to 0 degrees C, it develops intrinsic catalytic activity without cleavage of the prosegment.(ABSTRACT TRUNCATED AT 250 WORDS)