GERBIL ADRENAL 11-BETA-HYDROXYLATING AND 19-HYDROXYLATING ACTIVITIES RESPOND SIMILARLY TO INHIBITORY OR STIMULATORY AGENTS - 2 ACTIVITIES OF A SINGLE ENZYME
GERBIL ADRENAL 11-BETA-HYDROXYLATING AND 19-HYDROXYLATING ACTIVITIES RESPOND SIMILARLY TO INHIBITORY OR STIMULATORY AGENTS - 2 ACTIVITIES OF A SINGLE ENZYME
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DOI：
10.1016/0022-4731(88)90164-1
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发表时间：
1988-06-01
影响因子：
4.1
通讯作者：
MCCARTHY, JL
中科院分区：
文献类型：
--
作者：
DRUMMOND, TD;MASON, JI;MCCARTHY, JL
沙鼠(Meriones unguiculatus)的肾上腺线粒体表现出高水平的类固醇19-羟基化，这解释了该物种产生几乎等量的皮质酮和19-羟基皮质酮的能力(Proc.Soc.exp.Biol.Med.165(1980)69-74)。类固醇生成抑制剂和抗牛细胞色素 P-45011.beta 的多克隆抗体。用于确定这些药物是否会在体外对沙鼠肾上腺线粒体的 19-vs 11.β-羟基化产生差异或平行抑制。测试的抑制剂(0.1-60μM)(按照有效性递减的顺序列出)是咪唑利、美替拉酮、咪康唑和4-羟基雄烯二酮。对于每种抑制剂，11β-羟基化的抑制程度伴随着19-羟基化的平行下降。多克隆抗体制剂的添加也导致两个羟基化反应速率的同等下降。将ACTH 1μM添加到沙鼠肾上腺细胞的原代培养物中导致11β-和19-羟基化类固醇向培养基中的分泌几乎相等的增加。这些结果支持这样的假设：沙鼠肾上腺线粒体的11β-羟化酶具有以几乎相同的能力进行11β-和19-羟化的能力。
A high level of steroid 19-hydroxylation is exhibited by adrenal mitochondria of the gerbil, Meriones unguiculatus, that accounts for the ability of that species to produce nearly equal amounts of corticosterone and 19-hydroxycorticosterone (Proc. Soc. exp. Biol. Med. 165 (1980) 69-74). Inhibitors of steroidogenesis and a polyclonal antibody against bovine cytochrome P-45011.beta. were used to determine if the agents would effect differential or parallel suppression of 19-vs 11.beta.-hdyroxylation by gerbil adrenal mitochondria in vitro. The inhibitors (0.1-60 .mu.M) tested (listed in order of decreasing effectiveness) were imizalil, metyrapone, miconazole and 4-hydroxyandrostenedione. With each inhibitor the degree of suppression of 11.beta.-hydroxylation was accompanied by a parallel decline in 19-hydroxylation. The addition of the polyclonal antiody preparation also produced equivalent declines in the rates of the two hydroxylation reactions. The addition of ACTH 1 .mu.M to primary cultures of gerbil adrenal cells brought about nearly equal increases in the secretion of 11.beta.- and 19-hydroxylated steroids into the culture media. These results support the hypothesis that the 11.beta.-hydroxylase of gerbil adrenal mitochondria has the capacity to carryout 11.beta.- and 19-hydroxylations with nearly equal facility.