We have previously shown that detectable metabolism of cortisol to cortisone by 11β-hydroxysteroid dehydrogenase (11βHSD) 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 11β-HSD activities of granulosa-lutein cells obtained from individual follicles in relation to oocyte maturity and (2) whether the 11βHSD activity of pooled granulosa-lutein cells reflects the 11βHSD activities of the individual follicles for a given patient. 11βHSD activities were measured in intact cells in serum-free medium by a radiometric conversion assay (100 nmol/l [ 3H]cortisol to [3H]cortisone). Follicular 11βHSD 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 11βHSD 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 11βHSD 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 4 h respectively). Likewise, the 11βHSD activities of two independent multi-patient pools of cells were significantly lower than the mean values of the 11βHSD activities of the appropriate individual patients. We conclude that ovarian 11βHSD activity varies between follicles and that co-culture of granulosa-lutein cells with low enzyme activity can suppress the ovarian 11βHSD 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 11βHSD activity in human granulosa-lutein cells.
Journal of Endocrinology (1996) 148, 419–425
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