Yaguchi H, Tsutsumi K, Shimono K, Omura M, Sasano H, Nishikawa T
Otsuka Pharmaceutical Factory, Inc., Naruto Tokushima, Japan.
Life Sci. 1998;62(16):1387-95. doi: 10.1016/s0024-3205(98)00077-0.
Adrenocorticosteroids are known to be synthesized from cholesterol which may arise from de novo synthesis or from the uptake of low-density lipoproteins (LDL) or high-density lipoproteins (HDL). LDL is reported to be a main substrate for corticosteroid synthesis by bovine adrenocortical cells, although the role of HDL, which is well known to be used for steroid biosynthesis in rat adrenals, is still obscure. Therefore, we examined the role of HDL in the regulation of corticosteroidogenesis in bovine adrenals in order to clarify whether or not HDL was selectively utilized for corticosteroid synthesis in vitro. The present data demonstrated that HDL and LDL increased cortisol production in a dose-dependent manner in bovine adrenocortical cells in vitro, and also that HDL cholesterol increased cortisol production significantly higher than LDL cholesterol did. Addition of adrenocorticotrophic hormone (ACTH) with HDL to the incubation media enhanced much higher cortisol production than that with LDL in short time incubation. The present data also demonstrated that uptake of 125I-HDL was significantly greater than that of 125I-LDL. Thus, HDL rather than LDL is thought to be the preferred lipoprotein as a source of steroidogenic substrate cholesterol in bovine adrenal fasciculo-reticularis cells.
已知肾上腺皮质类固醇由胆固醇合成,胆固醇可能来源于从头合成,或来源于低密度脂蛋白(LDL)或高密度脂蛋白(HDL)的摄取。据报道,LDL是牛肾上腺皮质细胞合成皮质类固醇的主要底物,尽管众所周知HDL在大鼠肾上腺中用于类固醇生物合成,但其作用仍不清楚。因此,我们研究了HDL在牛肾上腺皮质类固醇生成调节中的作用,以阐明HDL在体外是否被选择性地用于皮质类固醇合成。目前的数据表明,在体外培养的牛肾上腺皮质细胞中,HDL和LDL均以剂量依赖的方式增加皮质醇的产生,并且HDL胆固醇比LDL胆固醇显著更高地增加皮质醇的产生。在短时间孵育中,将促肾上腺皮质激素(ACTH)与HDL添加到孵育培养基中比与LDL添加时增强更高的皮质醇产生。目前的数据还表明,125I-HDL的摄取显著大于125I-LDL的摄取。因此,在牛肾上腺束状带-网状带细胞中,HDL而非LDL被认为是作为类固醇生成底物胆固醇来源的首选脂蛋白。