Human ovarian theca cells are a source of renin

Human ovarian follicular fluid contains renin-like activity. In normal women, circulating levels of prorenin, the biosynthetic precursor of renin (EC 3.4.23.15), change in parallel with changes in progesterone during the menstrual cycle. Therefore, the ovary has been implicated as a source of plasma prorenin. In the present studies, we report the finding of high concentrations of prorenin in human ovarian follicular fluid (3000 ng.ml-1.hr-1 vs. 10-40 ng.ml-1.hr-1 in normal human plasma) obtained from follicles of women prepared for in vitro fertilization. The inactive renin-like enzyme was identified as prorenin by its activation characteristics, its molecular weight of 47,000, which is the same as that for recombinant prorenin, and its cross-reactivity with human renal renin antibodies. Culture of isolated human theca cells and isolated granulosa cells indicated that prorenin is secreted by theca cells but not by granulosa cells. Prorenin production by theca cells peaked during the first 10 days of culture and gradually decreased by 17 days. Active renin levels were 10% or less of the prorenin levels. Prorenin was barely detectable in medium from granulosa cells cultured for 24 days. Immunohistochemical staining of human ovaries (n = 5) with anti-human renin antibody demonstrated the presence of renin primarily in theca cells. These studies suggest that the theca cell is the source of the large quantities of prorenin in human ovarian follicular fluid.