High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C
High density lipoprotein as a source of cholesterol for adrenal steroidogenesis: a study in individuals with low plasma HDL-C
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DOI：
10.1194/jlr.p033449
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发表时间：
2013-06-01
影响因子：
6.5
通讯作者：
Stroes, Erik S. G.
中科院分区：
文献类型：
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作者：
Bochem, Andrea E.;Holleboom, Adriaan G.;Stroes, Erik S. G.
很少有研究涉及将脂蛋白衍生的胆固醇输送到肾上腺以产生类固醇的问题。虽然有证据反对低密度脂蛋白(LDL)的作用，但高密度脂蛋白(HDL)是否有助于肾上腺类固醇的生成尚不清楚。为了研究这一点，研究了患有ATP结合盒转运体A1(ABCA1)(n=24)、卵磷脂：胆固醇酰基转移酶(LCAT)(n=40)功能突变的男性受试者以及11名无ABCA1/LCAT突变的低高密度脂蛋白胆固醇(HDLC)受试者的尿中类固醇激素谱。与对照组(均为P<；0.001)相比，ABCA1、LCAT和低高密度脂蛋白胆固醇组的高密度脂蛋白胆固醇水平降低了39%。在所有低高密度脂蛋白胆固醇水平的组中，尿中17-酮类固醇的排泄量分别比对照组减少了33%、27%和32%(均P<；0.04)。在七种突变类型的携带者中，促肾上腺皮质激素(ACTH)刺激并未显示出与正常血脂对照组的差异。总而言之，这项研究表明，基础但未被刺激的皮质类固醇代谢在低高密度脂蛋白胆固醇受试者中减弱，与其分子来源无关。这些发现支持了高密度脂蛋白在人类基础肾上腺类固醇合成中作为胆固醇供体的作用。
Few studies have addressed the delivery of lipoprotein-derived cholesterol to the adrenals for steroid production in humans. While there is evidence against a role for low-density lipoprotein (LDL), it is unresolved whether high density lipoprotein (HDL) contributes to adrenal steroidogenesis. To study this, steroid hormone profiles in urine were assessed in male subjects suffering from functional mutations in ATP binding cassette transporter A1 (ABCA1) (n = 24), lecithin: cholesterol acyltransferase (LCAT) (n = 40), as well as in 11 subjects with low HDL cholesterol (HDL-C) without ABCA1/LCAT mutations. HDL-C levels were 39% lower in the ABCA1, LCAT, and low HDL-C groups compared with controls (all P < 0.001). In all groups with low HDL-C levels, urinary excretion of 17-ketogenic steroids was reduced by 33%, 27%, and 32% compared with controls (all P < 0.04). In seven carriers of either type of mutation, adrenocorticotropic hormone (ACTH) stimulation did not reveal differences from normolipidemic controls. In conclusion, this study shows that basal but not stimulated corticosteroid metabolism is attenuated in subjects with low HDL-C, irrespective of its molecular origin. These findings lend support to a role for HDL as a cholesterol donor for basal adrenal steroidogenesis in humans.