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DHCR24,胆固醇合成的关键酶,作为小鼠肾上腺皮质内皮层的标记基因。

DHCR24, a Key Enzyme of Cholesterol Synthesis, Serves as a Marker Gene of the Mouse Adrenal Gland Inner Cortex.

机构信息

Department of Anatomy, Physiology & Pharmacology, College of Veterinary Medicine, Auburn University, Auburn, AL 36849, USA.

出版信息

Int J Mol Sci. 2023 Jan 4;24(2):933. doi: 10.3390/ijms24020933.

DOI:10.3390/ijms24020933
PMID:36674444
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9867314/
Abstract

Steroid hormones are synthesized through enzymatic reactions using cholesterol as the substrate. In steroidogenic cells, the required cholesterol for steroidogenesis can be obtained from blood circulation or synthesized de novo from acetate. One of the key enzymes that control cholesterol synthesis is 24-dehydrocholesterol reductase (encoded by ). In humans and rats, DHCR24 is highly expressed in the adrenal gland, especially in the zona fasciculata. We recently reported that DHCR24 was expressed in the mouse adrenal gland's inner cortex and also found that thyroid hormone treatment significantly upregulated the expression of in the mouse adrenal gland. In the present study, we showed the cellular expression of DHCR24 in mouse adrenal glands in early postnatal stages. We found that the expression pattern of DHCR24 was similar to the X-zone marker gene 20αHSD in most developmental stages. This finding indicates that most steroidogenic adrenocortical cells in the mouse adrenal gland do not synthesize cholesterol locally. Unlike the 20αHSD-positive X-zone regresses during pregnancy, some DHCR24-positive cells remain present in parous females. Conditional knockout mice showed that the removal of in steroidogenic cells did not affect the overall development of the adrenal gland or the secretion of corticosterone under acute stress. Whether DHCR24 plays a role in conditions where a continuous high amount of corticosterone production is needed requires further investigation.

摘要

甾体激素是通过胆固醇作为底物的酶促反应合成的。在甾体生成细胞中,用于甾体生成的所需胆固醇可以从血液循环中获得,或者从头合成自乙酸盐。控制胆固醇合成的关键酶之一是 24-去氢胆固醇还原酶(由 编码)。在人和大鼠中,DHCR24 在肾上腺中高度表达,特别是在束状带。我们最近报道 DHCR24 在小鼠肾上腺的内皮质中表达,并发现甲状腺激素治疗显著上调了小鼠肾上腺中 的表达。在本研究中,我们展示了 DHCR24 在早期产后阶段的小鼠肾上腺中的细胞表达。我们发现,DHCR24 的表达模式与大多数发育阶段的 X-区标记基因 20αHSD 相似。这一发现表明,小鼠肾上腺中的大多数甾体生成性肾上腺皮质细胞并不在局部合成胆固醇。与 20αHSD 阳性的 X-区在妊娠期间退化不同,一些 DHCR24 阳性细胞在多产雌性中仍然存在。条件性敲除小鼠表明,在甾体生成细胞中敲除 不会影响肾上腺的整体发育或急性应激下的皮质酮分泌。DHCR24 是否在需要持续大量皮质酮产生的情况下发挥作用,需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/7866fdb6fc96/ijms-24-00933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/66262f451ddc/ijms-24-00933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/57ffc5803ec4/ijms-24-00933-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/b8c92848b71d/ijms-24-00933-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/eff0fb2894b0/ijms-24-00933-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/7866fdb6fc96/ijms-24-00933-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/66262f451ddc/ijms-24-00933-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/57ffc5803ec4/ijms-24-00933-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/9eb20ff96b96/ijms-24-00933-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1eb0/9867314/b8c92848b71d/ijms-24-00933-g004.jpg
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Single-cell molecular profiling of all three components of the HPA axis reveals adrenal ABCB1 as a regulator of stress adaptation.对下丘脑-垂体-肾上腺(HPA)轴所有三个组成部分的单细胞分子分析揭示,肾上腺ABCB1是应激适应的调节因子。
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