Michael A E, Gregory L, Thaventhiran L, Antoniw J W, Cooke B A
Department of Biochemistry and Molecular Biology, Royal Free Hospital School of Medicine, University of London, UK.
J Endocrinol. 1996 Mar;148(3):419-25. doi: 10.1677/joe.0.1480419.
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 [3H]cortisol to [3H]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 4 h 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.
我们之前已经表明，在人颗粒黄体细胞中，11β-羟类固醇脱氢酶（11βHSD）可将皮质醇代谢为可的松，这种可检测到的代谢与每位患者从所有抽吸的卵泡中汇集的颗粒黄体细胞有关，且与体外受精和胚胎移植的受孕失败相关。本研究的目的是评估：（1）从单个卵泡获得的颗粒黄体细胞中11βHSD活性的变化与卵母细胞成熟度的关系；（2）汇集的颗粒黄体细胞的11βHSD活性是否反映了给定患者单个卵泡的11βHSD活性。通过放射转化测定法（将100 nmol/L [3H]皮质醇转化为[3H]可的松）在无血清培养基中的完整细胞中测量11βHSD活性。卵泡的11βHSD活性范围为每4小时<10（检测不到）至514 pmol/mg蛋白质（n = 12例患者的105个卵泡），且与卵母细胞成熟度无关。在三名不同的患者中，卵泡的11βHSD活性范围为每4小时<10至117 pmol/mg蛋白质（n = 8个卵泡）、19至514 pmol/mg每4小时（n = 9个）和60至390 pmol/mg每4小时（n = 8个）。相应的多卵泡细胞池的11βHSD活性分别为每4小时<10、<10和44 pmol/mg，所有这些均显著低于单个卵泡中活性的算术平均值（分别为每4小时52、132和215 pmol/mg）。同样，两个独立的多患者细胞池的11βHSD活性显著低于相应个体患者的11βHSD活性平均值。我们得出结论，卵巢11βHSD活性在卵泡之间存在差异，并且低酶活性的颗粒黄体细胞共培养可以抑制来自不同卵泡（或患者）的细胞中具有高皮质醇代谢率的卵巢11βHSD活性。因此，这些数据表明人颗粒黄体细胞中卵巢11βHSD活性存在旁分泌抑制的可能性。
