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 cor tisone by 11 Beta-hydroxysteroid dehydrogenase (11 beta HSD) in human granulosa-lutein cells, pooled for each patient from all aspirated ova rian follicles, is associated with failure to conceive by in vitro fer tilization and embryo transfer. The aims of the present study were to assess: (1) the variation in the 11 beta HSD activities of granulosa-l utein cells obtained from individual follicles in relation to oocyte m aturity and (2) whether the 11 beta HSD activity of pooled granulosa-l utein cells reflects the 11 beta HSD activities of the individual foll icles for a given patient. 11 beta HSD activities were measured in int act cells in serum-free medium by a radiometric conversion assay (100 nmol/l [H-3]cortisol to [H-3]cortisone). Follicular 11 beta HSD activi ties ranged from <10 (undetectable) to 514 pmol/mg protein per 4 h (n= 105 follicles from 12 patients) and did not correlate with oocyte matu rity. In three separate patients, the follicular 11 beta HSD activitie s ranged from <10 to 117 pmol/mg protein per 4 h (n=8 follicles), 19 t o 514 pmol/mg per 4 h (n=9) and 60 to 390 pmol/mg per 4 h (n=8). The 1 1 beta HSD activities of the corresponding multi-follicular pools of c ells were <10, <10 and 44 pmol/mg per 4 h respectively, all of which w ere significantly lower (P<0.05) than the arithmetic means for the act ivities in the individual follicles (52, 132 and 215 pmol/mg per 4h re spectively). Likewise, the 11 beta HSD activities of two independent m ulti-patient pools of cells were significantly lower than the mean val ues of the 11 beta HSD activities of the appropriate individual patien ts. We conclude that ovarian 11 beta HSD activity varies between folli cles and that co-culture of granulosa-lutein cells with low enzyme act ivity can suppress the ovarian 11 beta HSD activity in cells from diff erent follicles (or patients) with high rates of cortisol metabolism. Hence, these data indicate the potential for paracrine inhibition of o varian 11 beta HSD activity in human granulosa-lutein cells.