Delaney M L, Melby J C
Section of Endocrinology and Metabolism, Evans Medical Foundation, University Hospital, Boston University Medical Center, Massachusetts 02118, USA.
Steroids. 1995 Mar;60(3):265-7. doi: 10.1016/0039-128x(94)00050-m.
19-Acetylenic-deoxycorticosterone (19-A-DOC) is believed to be a competitive irreversible inhibitor of the synthesis of 19-nor-deoxycorticosterone (19-nor-DOC), a potent mineralocorticoid implicated in some forms of human and animal hypertension. It has been shown to inactivate 11 beta/19-hydroxylase in hamster adrenal mitochondria. Dispersed bovine zona fasciculata cells were incubated for one hour with 1.5 x 10(-8) M ACTH and 0, 1, 10, or 100 microM 19-A-DOC and tritiated deoxycorticosterone (DOC) substrate. Steroids were separated using two sequential thin-layer chromatography systems and their tritium content was counted and corrected for recovery. The 19-A-DOC decreased synthesis of 19-hydroxydeoxycorticosterone, the precursor of 19-nor-DOC. The inhibitor also impaired 11-hydroxylation of DOC to form corticosterone. The data suggest that 19-A-DOC is an effective inhibitor of 11 beta/19-hydroxylase activity in dispersed bovine adrenal cells.
19-乙炔基脱氧皮质酮（19-A-DOC）被认为是19-去甲脱氧皮质酮（19-nor-DOC）合成的竞争性不可逆抑制剂，19-nor-DOC是一种强效盐皮质激素，与某些形式的人类和动物高血压有关。研究表明，它能使仓鼠肾上腺线粒体中的11β/19-羟化酶失活。将分散的牛束状带细胞与1.5×10⁻⁸ M促肾上腺皮质激素（ACTH）以及0、1、10或100 μM的19-A-DOC和氚标记的脱氧皮质酮（DOC）底物一起孵育1小时。使用两个连续的薄层色谱系统分离类固醇，并对其氚含量进行计数并校正回收率。19-A-DOC降低了19-去甲脱氧皮质酮前体19-羟基脱氧皮质酮的合成。该抑制剂还损害了DOC的11-羟化作用以形成皮质酮。数据表明，19-A-DOC是分散的牛肾上腺细胞中11β/19-羟化酶活性的有效抑制剂。
