The role of sterol carrier protein 2 in stimulation of steroidogenesis in rat adrenal mitochondria by adrenal cytosol.
The role of sterol carrier protein 2 in stimulation of steroidogenesis in rat adrenal mitochondria by adrenal cytosol.
复制标题
甾醇载体蛋白2在肾上腺胞质刺激大鼠肾上腺线粒体类固醇生成中的作用。
DOI：
10.1016/0003-9861(89)90349-4
复制
发表时间：
1989
影响因子：
3.9
通讯作者：
Jefcoate,CR
中科院分区：
文献类型：
--
作者：
McNamara,BC;Jefcoate,CR
促肾上腺皮质激素（ACTH）刺激可增强大鼠肾上腺线粒体胆固醇侧链裂解（CSCC）（8倍）。在体内，环己酰亚胺（CX）处理完全抑制了体内反应，并将体外细胞质刺激分解为：（i）ACTH敏感的，CX敏感的;（ii）ACTH敏感的，CX不敏感的;（iii）ACTH不敏感的，CX不敏感的。这些成分对促肾上腺皮质激素胞质溶胶的刺激作用大致相等。组分（i）和（iii）最可能对应于先前鉴定的胞质组分类固醇生成激活肽和固醇载体蛋白2（SCP 2）。SCP 2，通过放射免疫测定或刺激7-脱氢胆固醇还原酶的能力，没有升高肾上腺皮质激素治疗的肾上腺胞质溶胶或其他亚细胞组分。用抗SCP 2 IgG完全清除胞浆中的SCP 2，可使胞浆刺激活性降低，其增量与ACTH或CX治疗无关。加入一定量的SCP 2（相当于胞质溶胶中存在的SCP 2），可恢复SCP 2耗尽的胞质溶胶的活性，但单独或与完整胞质溶胶一起加入时没有效果，表明胞质溶胶中存在一种增强SCP 2作用的因子。纯肝SCP 2刺激CX线粒体CSCC的1.5- 2倍（EC 500.7 μm），但在肾上腺胞液中的效力比SCP 2低5倍。在这些制剂中，分别通过琥珀酸盐支持的活性和额外的异柠檬酸盐支持的活性来区分两个反应性胆固醇池。ACTH胞液和SCP 2均刺激胆固醇向线粒体P450 SCC的一部分的可用性，该部分被琥珀酸减少，但未能刺激仅由异柠檬酸产生的额外P450 SCC的可用性。
Cholesterol side-chain cleavage (CSCC) in isolated rat adrenal mitochondria is enhanced by prior corticotropin (ACTH) stimulationin vivo(8-fold). Part of this stimulation is retainedin vitroby addition of cytosol from ACTH-stimulated adrenals to mitochondria from unstimulated rats (2.5- to 6-fold).In vivocycloheximide (CX) treatment fully inhibits thein vivoresponse and resolves thein vitrocytosolic stimulation into components: (i) ACTH-sensitive, CX-sensitive; (ii) ACTH-sensitive, CX-insensitive; and (iii) ACTH-insensitive, CX-insensitive. These components contribute approximately equally to stimulation by ACTH cytosol. Components (i) and (iii) most probably correspond to previously identified cytosolic constituents Steroidogenesis activator peptide and sterol carrier protein 2 (SCP2). SCP2, as assayed by radioimmunoassay or ability to stimulate 7-dehydrocholesterol reductase, was not elevated in adrenal cytosol or other subcellular fractions by ACTH treatment. Complete removal of SCP2from cytosol by treatment with anti-SCP2IgG decreased cytosolic stimulatory activity by an increment that was independent of ACTH or CX treatment. Addition of an amount of SCP2, equivalent to that present in cytosol, restored activity to SCP2-depleted cytosol but had no effect alone or when added with intact cytosol, suggesting the presence of a factor in cytosol that potentiates SCP2action. Pure hepatic SCP2stimulated CX mitochondrial CSCC 1.5- to 2-fold (EC500.7 μm) but was five times less potent than SCP2in adrenal cytosol. Two pools of reactive cholesterol were distinguished in these preparations characterized, respectively, by succinate-supported activity and by additional isocitrate-supported activity. ACTH cytosol and SCP2each stimulated cholesterol availability to a fraction of mitochondrial P450sccthat was reduced by succinate but failed to stimulate availability to additional P450sccreduced only by isocitrate.