Disease relevance of Dhcr7

• In this paper, we also observed liver cell-specific sterol-mediated Dhcr7 gene induction in vitro by sterol depletion in rat hepatoma cells, suggesting the presence of sterol-mediated regulatory elements in the Dhcr7 gene [1].
• The cDNA encoding the 471-amino acid rat 7-dehydrocholesterol reductase (DHCR), an enzyme that has been implicated in both cholesterol biosynthesis and developmental abnormalities (e.g. Smith-Lemli-Opitz syndrome) in mammals, has been cloned and sequenced, and the primary structure of the enzyme has been deduced [2].
• In previous studies, early administration of the 7DHC-reductase inhibitor AY9944 to pregnant rats resulted in a high frequency of holoprosencephaly, relevant to craniofacial anomalies of SLOS [3].

Psychiatry related information on Dhcr7

• Smith-Lemli-Opitz syndrome (SLOS), an autosomal recessive condition with multiple malformations, mental retardation, and growth failure, results from markedly reduced activity of the final enzyme in the cholesterol biosynthetic pathway, 7-dehydrocholesterol reductase (DHCR7) [4].

High impact information on Dhcr7

• We believe that Dhcr7 is the first enzyme characterized with a sterol-regulatory function in the post-lanosterol pathway [1].
• Cholesterol biosynthesis from lanosterol. A concerted role for Sp1 and NF-Y-binding sites for sterol-mediated regulation of rat 7-dehydrocholesterol reductase gene expression [1].
• The 7-dehydrocholesterol reductase (Dhcr7) is the terminal enzyme in the pathway of cholesterol biosynthesis [1].
• Cholesterol biosynthesis from lanosterol. Molecular cloning, tissue distribution, expression, chromosomal localization, and regulation of rat 7-dehydrocholesterol reductase, a Smith-Lemli-Opitz syndrome-related protein [2].
• A detailed study on 7-DHCR expression in Leydig cells revealed that this enzyme plays a crucial role in steroidogenesis [5].

Biological context of Dhcr7

• Interestingly, human Dhcr7 gene in HepG2 cells produced no detectable isoform while mouse Dhcr7 gene in L929 cells produced three isoforms, suggesting a difference in alternative splicing between species [6].
• Unexpectedly, we have found the occurrence of at least five isoforms of Dhcr7, designated as Dhcr7-AS (alternatively spliced)-1 (1474 nts), -2 (1595 nts), -3 (1602 nts), -4 (1723 nts) and -5 (1287 nts), which was believed to be caused by alternative usage of three 5' noncoding exons [6].
• We previously reported that the Dhcr7 proximal promoter (-179 to +1), which contains CpG islands, is responsible for sterol-mediated expression of the rat gene [7].
• In the present study, we examined whether methylation of this region affects the transcriptional activity of the Dhcr7 gene [7].
• In vitro DNA methylation of the Dhcr7 promoter and luciferase-reporter assays showed that DNA methylation of the CpG islands suppressed transcription [7].

Anatomical context of Dhcr7

• 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 [8].

Associations of Dhcr7 with chemical compounds

• Thus, regulation of Dhcr7 through the combined mechanisms of tissue-specific transcription and differential alternative splicing appears unique among enzymes characterized from the entire post-lanosterol pathway in cholesterol biosynthesis [6].
• Furthermore, treatment of the methylated Dhcr7 promoter with the demethylating agent, 5-aza-2'-deoxycytidine (5-Aza-CdR), reversed the suppression of promoter activity [7].
• The enzyme 7-dehydrocholesterol reductase (Dhcr7) catalyzes the reduction of 7-dehydrocholesterol (DHC), the terminal reaction of the pathway of cholesterol biosynthesis [6].
• Treatment of pregnant rats with inhibitors of 7-DHC reductase, either AY9944 or BM15.766, has provided a valuable model to study the pathogenesis in SLOS [9].
• Low VE intake resulted in the consistent up-regulation of 7-dehydrocholesterol reductase and GATA binding protein 4, both involved in testosterone synthesis [10].

Other interactions of Dhcr7

• While Col IV alpha6 and RpL41 are known to be involved in cellular proliferation, mGST 1 and 7-DHCR are essential for normal Leydig cell steroidogenesis [5].

References