{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T22:15:30Z","timestamp":1783548930390,"version":"3.55.0"},"reference-count":38,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,5,1]]},"abstract":"<jats:p>We searched expressed sequence tag databases with conserved domains of the short-chain alcohol dehydrogenase superfamily and identified another isoform of 17\u03b2-hydroxysteroid dehydrogenase, 17\u03b2HSDXI. This enzyme converts 5\u03b1-androstane-3\u03b1, 17\u03b2-diol to androsterone. The substrate has been implicated in supporting gestation and modulating \u03b3-aminobutyric acid receptor activity. 17\u03b2HSDXI is colinear with human retinal short-chain dehydrogenase\/reductase retSDR2, a protein with no known biological activity (accession no. AAF06939). Of the proteins with known function, 17\u03b2HSDXI is most closely related to the retinol-metabolizing enzyme retSDR1, with which it has 30% identity. There is a polymorphic stretch of 15 adenosines in the 5\u2032 untranslated region of the cDNA sequence and a silent polymorphism at C719T. A 17\u03b2HSDXI construct with a stretch of 20 adenosines was found to produce significantly more enzyme activity than constructs containing 15 or less adenosines (43% vs. 26%, P &amp;lt; 0.005). The C719T polymorphism is present in 15% of genomic DNA samples. Northern blot analysis showed high levels of 17\u03b2HSDXI expression in the pancreas, kidney, liver, lung, adrenal, ovary, and heart. Immunohistochemical staining for 17\u03b2HSDXI is strong in steroidogenic cells such as syncytiotrophoblasts, sebaceous gland, Leydig cells, and granulosa cells of the dominant follicle and corpus luteum. In the adrenal 17\u03b2HSDXI, staining colocalized with the distribution of 17\u03b1-hydroxylase but was stronger in the mid to outer cortex. 17\u03b2HSDXI was also found in the fetus and increased after birth. Liver parenchymal cells and epithelium of the endometrium and small intestine also stained. Regulation studies in mouse Y1 cells showed that cAMP down-regulates 17\u03b2HSDXI enzymatic activity (40% vs. 32%, P &amp;lt; 0.05) and reduces gene expression to undetectable levels. All-trans-retinoic acid did not affect 17\u03b2HSDXI expression or activity, but addition of the retinoid together with cAMP significantly decreased activity over cAMP alone (32% vs. 23%, P &amp;lt; 0.05). Cloning and sequencing of the 17\u03b2HSDXI promoter identified the potential nuclear receptor steroidogenic factor-1 half-site TCCAAGGCCGG, and a cluster of three other potential steroidogenic factor-1 half-sites were found in the distal part of intron 1. Collectively, these results suggest a role for 17\u03b2HSDXI in androgen metabolism during steroidogenesis and a possible role in nonsteroidogenic tissues including paracrine modulation of 5\u03b1-androstane-3\u03b1, 17\u03b2-diol levels. 17\u03b2HSDXI could act by metabolizing compounds that stimulate steroid synthesis and\/or by generating metabolites that inhibit it.<\/jats:p>","DOI":"10.1210\/en.2002-221030","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T23:43:40Z","timestamp":1050450220000},"page":"2084-2091","source":"Crossref","is-referenced-by-count":55,"title":["17\u03b2-Hydroxysteroid Dehydrogenase Type XI Localizes to Human Steroidogenic 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