{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCYP3A7 is a key cytochrome P450 enzyme that is predominantly expressed in the human fetal liver where it plays an essential role in steroid hormone metabolism. In the fetus, CYP3A7 catalyzes the 16α‐hydroxylation of dehydroepiandrosterone (DHEA), DHEA sulfate, and estrone, and is implicated in the metabolism of all‐trans retinoic acid. Although traditionally viewed as a fetal enzyme, genetic variants—most notably the CYP3A7*1C allele—lead to persistent expression in a subset of adults, thereby contributing significantly to total CYP3A activity in tissues such as the liver, endometrium, and placenta. Developmental studies in humans and mouse models further indicate that CYP3A7 expression is tightly regulated by nuclear receptors and epigenetic modifications during the transition from fetal to postnatal life."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "8"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn the context of drug metabolism, CYP3A7 displays distinct substrate selectivity and catalytic efficiency compared with its adult counterpart CYP3A4. Although it shares overlapping specificities with other CYP3A enzymes, CYP3A7 generally operates at lower metabolic rates—evident in its slower turnover of inhaled glucocorticoids and alternative binding modes in testosterone hydroxylation—and tends to favor oxidation reactions on substrates like deoxycholate at positions that differ from those preferred by CYP3A4. Moreover, polymorphisms influencing CYP3A7 expression have been shown to affect the pharmacokinetics of immunosuppressants such as tacrolimus and cyclosporine, while for other agents, such as clozapine, CYP3A7 variation does not appear to exert a substantial effect. These findings underscore that the CYP3A7 genotype contributes, alongside other CYP3A isoforms, to interindividual variability in drug clearance and, in certain cases, may also modulate clinical outcomes in oncology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "17"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond drug metabolism, CYP3A7’s activity in steroid clearance has broad implications for endocrine homeostasis and disease susceptibility. Its role in metabolizing DHEA(S) positions it as a modulator of adrenal androgen levels, influencing conditions such as polycystic ovary syndrome, while persistent CYP3A7 expression has been linked to altered estrogen metabolism in reproductive tissues and associations with bone mineral density in postmenopausal women. Novel variants (for example, CYP3A7.1L generated through alternative splicing with pseudogene CYP3AP1) further expand the functional diversity of this enzyme and may explain interethnic differences in xenobiotic and steroid hormone metabolism. Additionally, dysregulation of CYP3A7 expression, such as its marked downregulation observed in conditions like melanosis coli, hints at a broader relevance of this enzyme in pathology."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "22"}]}, {"type": "t", "text": ""}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Oliver Burk, Heike Tegude, Ina Koch, et al. 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