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Here, we delineate an unrecognized intestinal steroid\/bile acid regulatory axis that mechanistically links androgen suppression to extratumoral metabolic aberrations.\n                    <jats:italic>HSD3B1<\/jats:italic>\n                    is the most common inherited link to prostate cancer mortality and mediates its effects by regulating steroid metabolism. Integrated metabolomic profiling of patients undergoing ADT revealed a rapid genotype-associated reduction in circulating bile acids, most pronounced in carriers of the adrenal-permissive\n                    <jats:italic>HSD3B1<\/jats:italic>\n                    (1245C) allele. Surprisingly, analyses in human intestinal tissue and mechanistic investigations in in vitro models identified the terminal ileum as a unique site of\n                    <jats:italic>HSD3B1<\/jats:italic>\n                    and\n                    <jats:italic>SLC10A2<\/jats:italic>\n                    (ASBT) coexpression, where catalytically active 3\u03b2HSD1 is transcriptionally governed by liver receptor homolog-1 (LRH-1). Pharmacologic or genetic LRH-1 inhibition coordinately suppressed\n                    <jats:italic>HSD3B1<\/jats:italic>\n                    and\n                    <jats:italic>SLC10A2<\/jats:italic>\n                    expression and function, while inducing adaptive\n                    <jats:italic>HSD11B2<\/jats:italic>\n                    upregulation and enhanced glucocorticoid inactivation. This LRH-1\u2013dependent regulatory program persisted independently of androgen and glucocorticoid receptor signaling under in vitro conditions modeling androgen deprivation. These findings establish LRH-1 as a central integrator of intestinal steroidogenesis and bile acid transport and implicate the LRH-1\/\n                    <jats:italic>HSD3B1<\/jats:italic>\n                    \/\n                    <jats:italic>SLC10A2<\/jats:italic>\n                    network as a mechanistic driver of ADT-associated metabolic disturbances and a potential target for therapeutic intervention.\n                  <\/jats:p>","DOI":"10.1172\/jci202725","type":"journal-article","created":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T18:01:06Z","timestamp":1781460066000},"source":"Crossref","is-referenced-by-count":0,"title":["HSD3B1 links ileal steroid metabolism to bile acid regulation in patients with prostate cancer"],"prefix":"10.1172","volume":"136","author":[{"given":"Nikou","family":"Fotouhi","sequence":"first","affiliation":[{"name":"Desai Sethi Urology Institute and"},{"name":"Sylvester Comprehensive Cancer Center, University of Miami Miller School of 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