Leukocytes modulate 11 β-hydroxysteroid dehydrogenase (11 β-HSD) activity in human granulosa-lutein cell cultures

Abstract

It is well established that there are interactions between the immune and reproductive systems. The ovary contains indigenous macrophages, as well as other classes of leukocytes in smaller numbers. Cytokines secreted by these cells have been shown to have the ability to regulate ovarian steroidogenesis. In the present study, the effect of leukocytes on 11 β-hydroxysteroid dehydrogenase (11 β-HSD) in human granulosa-lutein cells was examined. In addition, individual cytokines were also tested for their ability to regulate this enzyme. The follicular aspirates of patients undergoing IVF treatment were used as a source of granulosa cells. Cells isolated from these aspirates were found to contain between 15 and 60% leukocytes as assessed by flow cytometry (FACS). Leukocytes were removed from the sample preparations by the use of immunomagnetic beads coated with CD45 antibody, which recognises a surface antigen on all classes of leukocyte. Removal of leukocytes significantly decreased the 11 β-HSD activity in the granulosa cells, assayed after 3 days of culture, from 7.3 (2–20) to 3.5 (1–10) pmol cortisone formed/50 000 cells/4 h (medians and ranges, n=15). Addition of IL-5 and IL-6 significantly increased the 11 β-HSD activity in granulosa cell cultures both in the presence and absence of leukocytes. Addition of IL-4 and IFN- γ increased ll β-HSD activity only in the leukocyte-depleted granulosa cell cultures, whereas IL-2 had no effect on either of the cultures. The data suggests that leukocytes interact with the ovarian cells through cytokine secretion and/or cell–cell contact to increase the 11 β-HSD activity in human granulosa cells.