Follicular variation in ovarian 11 beta-hydroxysteroid dehydrogenase (11 beta HSD) activities: Evidence for the paracrine inhibition of 11 beta HSD in human granulosa-lutein cells

We have previously shown that detectable metabolism of cortisol to cortisone by 11 Beta-hydroxysteroid dehydrogenase (11 beta HSD) in human granulosa-lutein cells, pooled for each patient from all aspirated ovarian follicles, is associated with failure to conceive by in vitro fertilization and embryo transfer. The aims of the present study were to assess: (1) the variation in the 11 beta HSD activities of granulosa-lutein cells obtained from individual follicles in relation to oocyte maturity and (2) whether the 11 beta HSD activity of pooled granulosa-lutein cells reflects the 11 beta HSD activities of the individual follicles for a given patient. 11 beta HSD activities were measured in intact cells in serum-free medium by a radiometric conversion assay (100 nmol/l [H-3]cortisol to [H-3]cortisone). Follicular 11 beta HSD activities ranged from <10 (undetectable) to 514 pmol/mg protein per 4 h (n=105 follicles from 12 patients) and did not correlate with oocyte maturity. In three separate patients, the follicular 11 beta HSD activities ranged from <10 to 117 pmol/mg protein per 4 h (n=8 follicles), 19 to 514 pmol/mg per 4 h (n=9) and 60 to 390 pmol/mg per 4 h (n=8). The 11 beta HSD activities of the corresponding multi-follicular pools of cells were <10, <10 and 44 pmol/mg per 4 h respectively, all of which were significantly lower (P<0.05) than the arithmetic means for the activities in the individual follicles (52, 132 and 215 pmol/mg per 4h respectively). Likewise, the 11 beta HSD activities of two independent multi-patient pools of cells were significantly lower than the mean values of the 11 beta HSD activities of the appropriate individual patients. We conclude that ovarian 11 beta HSD activity varies between follicles and that co-culture of granulosa-lutein cells with low enzyme activity can suppress the ovarian 11 beta HSD activity in cells from different follicles (or patients) with high rates of cortisol metabolism. Hence, these data indicate the potential for paracrine inhibition of ovarian 11 beta HSD activity in human granulosa-lutein cells.