Kraemer Fredric B, Shen Wen-Jun, Patel Shailja, Osuga Jun-Ichi, Ishibashi Shun, Azhar Salman
Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA.
Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E408-12. doi: 10.1152/ajpendo.00428.2006. Epub 2006 Sep 19.
Steroid hormones are synthesized using cholesterol as precursor. To determine the functional importance of the low density lipoprotein (LDL) receptor and hormone-sensitive lipase (HSL) in adrenal steroidogenesis, adrenal cells were isolated from control, HSL(-/-), LDLR(-/-), and double LDLR/HSL(-/-) mice. The endocytic and selective uptake of apolipoprotein E-free human high density lipoprotein (HDL)-derived cholesteryl esters did not differ among the mice, with selective uptake accounting for >97% of uptake. In contrast, endocytic uptake of either human LDL- or rat HDL-derived cholesteryl esters was reduced 80-85% in LDLR(-/-) and double-LDLR/HSL(-/-) mice. There were no differences in the selective uptake of either human LDL- or rat HDL-derived cholesteryl esters among the mice. Maximum corticosterone production induced by ACTH or dibutyryl cyclic AMP and lipoproteins was not altered in LDLR(-/-) mice but was reduced 80-90% in HSL(-/-) mice. Maximum corticosterone production was identical in HSL(-/-) and double-LDLR/HSL(-/-) mice. These findings suggest that, although the LDL receptor is responsible for endocytic delivery of cholesteryl esters from LDL and rat HDL to mouse adrenal cells, it appears to play a negligible role in the delivery of cholesterol for acute adrenal steroidogenesis in the mouse. In contrast, HSL occupies a vital role in adrenal steroidogenesis because of its link to utilization of selectively delivered cholesteryl esters from lipoproteins.
类固醇激素以胆固醇为前体进行合成。为了确定低密度脂蛋白（LDL）受体和激素敏感性脂肪酶（HSL）在肾上腺类固醇生成中的功能重要性，从对照小鼠、HSL基因敲除（-/-）小鼠、LDLR基因敲除（-/-）小鼠以及双基因敲除LDLR/HSL（-/-）小鼠中分离出肾上腺细胞。无载脂蛋白E的人高密度脂蛋白（HDL）衍生的胆固醇酯在这些小鼠中的内吞和选择性摄取没有差异，选择性摄取占摄取量的97%以上。相比之下，人LDL或大鼠HDL衍生的胆固醇酯在LDLR（-/-）和双基因敲除LDLR/HSL（-/-）小鼠中的内吞摄取减少了80 - 85%。在这些小鼠中，人LDL或大鼠HDL衍生的胆固醇酯的选择性摄取没有差异。促肾上腺皮质激素（ACTH）或二丁酰环磷酸腺苷（dibutyryl cyclic AMP）与脂蛋白诱导的最大皮质酮生成在LDLR（-/-）小鼠中没有改变，但在HSL（-/-）小鼠中减少了80 - 90%。HSL（-/-）小鼠和双基因敲除LDLR/HSL（-/-）小鼠中的最大皮质酮生成相同。这些发现表明，尽管LDL受体负责将LDL和大鼠HDL中的胆固醇酯通过内吞作用递送至小鼠肾上腺细胞，但它在为小鼠急性肾上腺类固醇生成递送胆固醇方面似乎起的作用微不足道。相比之下，HSL在肾上腺类固醇生成中起着至关重要的作用，因为它与从脂蛋白中选择性递送的胆固醇酯的利用有关。
