Abstract. The endocrinology of equine pregnancy is unique, but many of its unusual phenomena closely resemble pregnancy in women. Placental estrone synthes

Read the full paper: Compartmentalization of DHCR7 links 7-DHC metabolism to B-ring unsaturated steroid synthesis in the equine fetal gonad

Cholesterol biosynthesis is indispensable for CNS development and function. The developing brain relies almost entirely on intrinsic sterol synthesis to support membrane biogenesis, axonal outgrowth, synaptogenesis, and myelination. Pathogenic variants in sterol biosynthetic enzymes, including DHCR7 and DHCR24, result in complex neurodevelopmental disorders such as Smith-Lemli-Opitz syndrome and desmosterolosis. In addition to cholesterol-lowering drugs (statins), some other pharmacological agents such as antipsychotics, antidepressants, and beta blockers can also inhibit cholesterol biosynthesis due to off-target effects. This inhibition produces dual pathophysiological effects: cholesterol depletion and accumulation of its precursor, 7-dehydrocholesterol, an exceptionally oxidizable molecule that spontaneously generates toxic oxysterols. Given the intense demand for cholesterol synthesis in the developing brain, prenatal exposure to sterol biosynthesis–inhibiting medications may have far-reaching effects. In this Review, we describe convergent biochemical, genetic, and epidemiologic data that implicate developmental sterol dysregulation as a modifiable risk factor for neurodevelopmental pathology and underscore the urgent need for routine sterol pathway safety assessment in drug development and prenatal pharmacotherapy.

Nature Communications - Genotypes causing pregnancy loss and perinatal mortality are depleted among living individuals and are therefore difficult to find. Here, using genetic data for 1.52 million...

Smith-Lemli-Opitz Sendromu (SLOS), nadir görülen genetik bir metabolik ve gelişimsel bozukluktur. DHCR7 genindeki mutasyon sonucu vücudun kolesterol üretiminde sorun yaşanır. Bu durum hem fiziksel hem de zihinsel gelişim üzerinde etkiler yaratır. Sendrom, ilk kez 1964 yılında tanımlanmış olup otozomal resesif şekilde kalıtılır. SMITH-LEMLI-OPITZ SENDROMU BELİRTİLERİ Belirtiler kişiden kişiye farklılık gösterebilir. Hafif vakalarda sadece öğrenme güçlüğü görülebilirken, ağır vakalarda çoklu organ anomalileri ortaya çıkabilir.

Objective 7-Dehydrocholesterol reductase (DHCR7) is an enzyme that plays a crucial regulatory role in sterol biosynthesis and has been implicated in tumorigenesis and progression. This study aims to elucidate the biological function of DHCR7 in the pathogenesis of colorectal cancer (CRC). Methods By integrating multi-omics data (including public genomic databases and mass spectrometry data from clinical samples) and establishing in vivo and in vitro experimental systems (encompassing animal models and CRC cell lines with gene overexpression and knockdown), we systematically investigated the functional role of DHCR7 in CRC. A multimodal research strategy combining bioinformatics analysis with molecular biology experiments (Quantitative Real-Time Polymerase Chain Reaction (qRT-PCR), western blotting, immunohistochemistry, etc.), proteomics analysis (liquid chromatography–mass spectrometry), and cellular functional assays (proliferation, apoptosis, migration, and invasion) was employed. Results Elevated levels of sterols were observed in CRC tumor tissues, and high cholesterol levels were found to promote the malignant phenotype of tumor cells. Mass spectrometry revealed that DHCR7 was significantly upregulated in CRC tissues and correlated with poor clinical prognosis. DHCR7 could modulate the cholesterol levels in CRC cells; overexpression of this gene enhanced cell proliferation, inhibited apoptosis, and promoted invasion and migration. Conversely, inhibition of DHCR7 expression abrogated these pro-tumorigenic effects, which was consistent with the inactivation of the PI3K/AKT/mTOR signaling pathway and confirmed by pathway reactivation experiments. DHCR7 deficiency significantly reduced tumorigenicity in vivo. Conclusion DHCR7 regulates the progression of CRC both in vitro and in vivo through the PI3K/AKT/mTOR signaling axis and affects the cholesterol levels in CRC.

Cholesterol's Role in Cancer Progression and Drug Resistance A recent study published in Cell Death & Disease reveals a novel molecular mechanism linking cholesterol metabolism to tumor progression and therapy resistance in thyroid cancer. Researchers found that a decline in the protein RTN3 leads to the stabilization of DHCR7, a key enzyme in cholesterol synthesis. This results in increased intracellular cholesterol, which fuels tumor growth and, critically, induces insensitivity to MEK inhibitors, a class of targeted cancer drugs.

自治医科大学は、コレステロール合成経路の最終段階を担う酵素「DHCR7」の阻害がフェロトーシスを強力に抑制する作用があることを新たに発見したと発表した。