Carballeira A, Brown J W, Fishman L M, Bertetta C, Bossart G D
Research Service, Veterans Administration Medical Center, Miami, Florida 33125.
Gen Comp Endocrinol. 1987 Nov;68(2):304-12. doi: 10.1016/0016-6480(87)90042-6.
The effects of adrenocorticotropic hormone (ACTH), cyclic AMP (cAMP), NADPH, Krebs cycle intermediates (KCl), and metyrapone on the two key mitochondrial reactions in the biosynthesis of glucocorticoids--11 beta-hydroxylation and cholesterol cleavage--were studied in preparations from the adrenal glands of stranded whales (Kogia breviceps and Mesoplodon europaeus) and some terrestrial mammals. ACTH (30 pM) and cAMP (1.0 mM) enhanced the 11 beta-hydroxylation of [11-3H]deoxycorticosterone ([3H]DOC) in monolayer cultures of whale adrenal cells during a 4-hr incubation period. Mitochondria from whale and beef adrenals responded in a similar dose-related fashion to NADPH generated by the addition of increasing amounts of NADP (0-0.6 mM) to the in vitro system: at each level of NADPH, 11 beta-hydroxylation of [14C]DOC was several-fold greater than the cleavage of [14C]cholesterol. Metyrapone interfered in a dose-related manner with both the 11 beta-hydroxylation of [14C]DOC and the cleavage of [14C]cholesterol by mitochondria from whale and beef adrenals; inhibition of 11 beta-hydroxylation exceeded 60% at 0.1 mM metyrapone and was virtually complete at 1.0 mM in both species, while inhibition of [14C]cholesterol cleavage averaged 25% at 0.1 mM metyrapone and 50% at 1.0 mM. The effect of exogenous NADPH in supporting the 11 beta-hydroxylation of [14C]DOC could be maintained in beef and rat adrenal mitochondria to the extent of 70-100% by substitution with any of the KCl. This phenomenon was not found in similar whale studies where the KCl were all ineffective.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了促肾上腺皮质激素（ACTH）、环磷酸腺苷（cAMP）、还原型辅酶Ⅱ（NADPH）、三羧酸循环中间产物（KCl）和甲吡酮对搁浅鲸（小抹香鲸和欧洲中喙鲸）及一些陆生哺乳动物肾上腺中糖皮质激素生物合成的两个关键线粒体反应——11β-羟化和胆固醇裂解的影响。在4小时的孵育期内，ACTH（30 pM）和cAMP（1.0 mM）增强了鲸肾上腺细胞单层培养物中[11-³H]脱氧皮质酮（[³H]DOC）的11β-羟化。向体外系统中添加越来越多的烟酰胺腺嘌呤二核苷酸磷酸（NADP，0 - 0.6 mM）所产生的NADPH，使鲸和牛肾上腺的线粒体以类似的剂量相关方式作出反应：在每个NADPH水平，[¹⁴C]DOC的11β-羟化比[¹⁴C]胆固醇的裂解大几倍。甲吡酮以剂量相关的方式干扰了[¹⁴C]DOC的11β-羟化以及鲸和牛肾上腺线粒体对[¹⁴C]胆固醇的裂解；在0.1 mM甲吡酮时，两种动物中对11β-羟化的抑制超过60%，在1.0 mM时几乎完全抑制，而在0.1 mM甲吡酮时，[¹⁴C]胆固醇裂解的抑制平均为25%，在1.0 mM时为50%。通过用任何一种KCl替代，外源NADPH支持[¹⁴C]DOC的11β-羟化的作用在牛和大鼠肾上腺线粒体中可维持70 - 100%。在类似的鲸类研究中未发现这种现象，其中所有KCl均无效。（摘要截断于250字）
