{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n DHRS7, a member of the short‐chain dehydrogenase/reductase (SDR) superfamily, has emerged as a multifunctional enzyme that contributes to the metabolism of both endogenous signaling molecules and xenobiotics. Experimental studies employing purified protein and cell‐based assays have demonstrated that DHRS7 is an integral endoplasmic reticulum enzyme with NADPH‐dependent reducing activity toward substrates bearing carbonyl groups – including several steroids and retinoids—as well as industrial and environmental toxicants."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "5"}]}, {"type": "t", "text": " In particular, DHRS7 catalyzes the conversion of cortisone into 20β‐dihydrocortisone and the reduction of 5α‐dihydrotestosterone to 3α‐androstanediol, thereby modulating androgen receptor signaling. In vivo analyses in castration‐resistant prostate cancer (CRPC) further underscore a role for DHRS7 in steroid metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}, {"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Notably, reduced expression of DHRS7 has been associated with higher tumor grade in prostate cancer, and experimental knockdown studies have shown that loss of DHRS7 promotes increased cell proliferation, enhanced migration, and diminished cell adhesion – features that support a tumor‐suppressive function in this tissue."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": " Beyond prostate cancer, genetic association studies nominate DHRS7 as a candidate influencing age at smoking initiation, suggesting its potential involvement in nicotine metabolism."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "8"}]}, {"type": "t", "text": " Moreover, differential expression of DHRS7 has been observed in hepatic models – with marked upregulation during liver regeneration and in fatty liver conditions – and it is incorporated into prognostic gene signatures for gastric adenocarcinoma."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "9", "end_ref": "11"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In addition, expression studies in non‐mammalian species suggest an evolutionarily conserved role for DHRS7 (or its homologs) in metabolic regulation across diverse taxa."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "5"}, {"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": " Finally, high‐throughput transcriptomic analysis during rat liver regeneration revealed a dramatic upregulation of DHRS7 expression – with levels increasing over 968‐fold compared to control – further highlighting its potential contribution to metabolic adaptation in response to cellular injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Collectively, these results define DHRS7 as a cytoplasmically oriented SDR enzyme with dual substrate specificity that is central to both steroid and xenobiotic metabolism; alterations in its expression may influence carcinogenesis and metabolic regulation in multiple tissues"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "–."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": "\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Hana Stambergova, Lucie Skarydova, James E Dunford, et al. 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