{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T03:57:38Z","timestamp":1792727858565,"version":"4.5.0"},"reference-count":54,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:00:00Z","timestamp":1727827200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002241","name":"Japan Science and Technology Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100002241","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004330","name":"Smoking Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100004330","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007325","name":"Kobayashi International Scholarship Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100007325","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>3\u03b2-Hydroxysteroid dehydrogenases (3\u03b2-HSDs) catalyze the oxidative conversion of delta (5)-ene-3-beta-hydroxy steroids and ketosteroids. Human 3\u03b2-HSD type 2 (HSD3B2) is predominantly expressed in gonadal and adrenal steroidogenic cells for producing all classes of active steroid hormones. Mutations in HSD3B2 gene cause a rare form of congenital adrenal hyperplasia with varying degree of salt wasting and incomplete masculinization, resulting from reduced production of corticoids and androgens. Therefore, evaluation of the HSD3B2 enzymatic activity in both pathways for each steroid hormone production is important for accurately understanding and diagnosing this disorder. Using progesterone receptor (PR)- and androgen receptor (AR)-mediated transactivation, we adapted a method that easily evaluates enzymatic activity of HSD3B2 by quantifying the conversion from substrates [pregnenolone (P5) and dehydroepiandrosterone (DHEA)] to (progesterone and androstenedione). HEK293 cells were transduced to express human HSD3B2, and incubated medium containing P5 or DHEA. Depending on the incubation time with HSD3B2-expressing cells, the culture media progressively increased luciferase activities in CV-1 cells, transfected with the PR\/AR expression vector and progesterone-\/androgen-responsive reporter. Culture media from human and other mammalian HSD3B1-expressing cells also increased the luciferase activities. HEK293 cells expressing various missense mutations in the HSD3B2 gene revealed the potential of this system to evaluate the relationship between the enzymatic activities of mutant proteins and patient phenotype.<\/jats:p>","DOI":"10.3389\/fendo.2024.1480722","type":"journal-article","created":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:31:20Z","timestamp":1727829080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":8,"title":["Evaluation of 3\u03b2-hydroxysteroid dehydrogenase activity using progesterone and androgen receptors-mediated transactivation"],"prefix":"10.3389","volume":"15","author":[{"given":"Takashi","family":"Yazawa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yugo","family":"Watanabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuko","family":"Yokohama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Imamichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuya","family":"Hasegawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke-ichi","family":"Nakajima","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takeshi","family":"Kitano","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takanori","family":"Ida","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takahiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Sayful","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Umezawa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoru","family":"Takahashi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuhito","family":"Kato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharmin","family":"Jahan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun-ichi","family":"Kawabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,10,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2017.09.002","article-title":"Steroidogenesis: unanswered questions","volume":"28","author":"Miller","year":"2017","journal-title":"Trends Endocrinol metabolism: TEM"},{"key":"B2","doi-asserted-by":"publisher","first-page":"81","DOI":"10.1210\/er.2010-0013","article-title":"The molecular biology, biochemistry, and physiology of human steroidogenesis and its disorders","volume":"32","author":"Miller","year":"2011","journal-title":"Endocrine Rev"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1210\/er.2002-0050","article-title":"Molecular biology of the 3beta-hydroxysteroid dehydrogenase\/delta5-delta4 isomerase gene family","volume":"26","author":"Simard","year":"2005","journal-title":"Endocrine Rev"},{"key":"B4","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/bs.vh.2018.05.002","article-title":"Mutation of HSD3B2 gene and fate of dehydroepiandrosterone","volume":"108","author":"Baquedano","year":"2018","journal-title":"Vitamins hormones"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1006\/geno.1999.5459","article-title":"Cloning, expression, and physical mapping of the 3beta-hydroxysteroid dehydrogenase gene cluster (HSD3BP1-HSD3BP5) in human","volume":"61","author":"McBride","year":"1999","journal-title":"Genomics"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1210\/mend-3-8-1310","article-title":"Full length cDNA structure and deduced amino acid sequence of human 3 beta-hydroxy-5-ene steroid dehydrogenase","volume":"3","author":"Luu The","year":"1989","journal-title":"Mol Endocrinol (Baltimore Md.)"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/s1470-2045(16)30227-3","article-title":"HSD3B1 and resistance to androgen-deprivation therapy in prostate cancer: a retrospective, multicohort study","volume":"17","author":"Hearn","year":"2016","journal-title":"Lancet Oncol"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2017.0147","article-title":"Independent validation of effect of HSD3B1 genotype on response to androgen-deprivation therapy in prostate cancer","volume":"3","author":"Agarwal","year":"2017","journal-title":"JAMA Oncol"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1210\/en.2019-00366","article-title":"HSD3B1 genotypes conferring adrenal-restrictive and adrenal-permissive phenotypes in prostate cancer and beyond","volume":"160","author":"Sabharwal","year":"2019","journal-title":"Endocrinology"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1245\/s10434-022-12088-w","article-title":"Association of HSD3B1 genotype and clinical outcomes in postmenopausal estrogen-receptor-positive breast cancer","volume":"29","author":"Flanagan","year":"2022","journal-title":"Ann Surg Oncol"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.steroids.2021.108937","article-title":"Association of genetic polymorphisms with local steroid metabolism in human benign breasts","volume":"177","author":"Lee","year":"2022","journal-title":"Steroids"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1002\/pros.24504","article-title":"Prospective role of 3\u03b2HSD1 in prostate cancer precision medicine","volume":"83","author":"Zhuang","year":"2023","journal-title":"Prostate"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1530\/erc-24-0023","article-title":"Importance of 3\u03b2-hydroxysteroid dehydrogenases and their clinical use in prostate cancer","volume":"31","author":"Shiota","year":"2024","journal-title":"Endocrine-related Cancer"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1210\/mend-5-8-1147","article-title":"Structure and expression of a new complementary DNA encoding the almost exclusive 3 beta-hydroxysteroid dehydrogenase\/delta 5-delta 4-isomerase in human adrenals and gonads","volume":"5","author":"Rh\u00e9aume","year":"1991","journal-title":"Mol Endocrinol (Baltimore Md.)"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.3390\/diagnostics12092168","article-title":"Approach of heterogeneous spectrum involving 3beta-hydroxysteroid dehydrogenase 2 deficiency","volume":"12","author":"Nicola","year":"2022","journal-title":"Diagnostics (Basel Switzerland)"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1007\/s12020-018-01835-3","article-title":"Clinical perspectives in congenital adrenal hyperplasia due to 3\u03b2-hydroxysteroid dehydrogenase type 2 deficiency","volume":"63","author":"Al Alawi","year":"2019","journal-title":"Endocrine"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2019.105493","article-title":"Evaluation of 17\u03b2-hydroxysteroid dehydrogenase activity using androgen receptor-mediated transactivation","volume":"196","author":"Yazawa","year":"2020","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1002\/mrd.23163","article-title":"Cyclooxygenase-2 is acutely induced by CCAAT\/enhancer-binding protein beta to produce prostaglandin E 2 and F 2alpha following gonadotropin stimulation in Leydig cells","volume":"86","author":"Yazawa","year":"2019","journal-title":"Mol Reprod Dev"},{"key":"B19","doi-asserted-by":"publisher","first-page":"1611","DOI":"10.1038\/s41598-023-28814-7","article-title":"Expression of Chrna9 is regulated by Tbx3 in undifferentiated pluripotent stem cells","volume":"13","author":"Yazawa","year":"2023","journal-title":"Sci Rep"},{"key":"B20","doi-asserted-by":"publisher","first-page":"8374","DOI":"10.1038\/s41598-017-08780-7","article-title":"Diethylstilbestrol administration inhibits theca cell androgen and granulosa cell estrogen production in immature rat ovary","volume":"7","author":"Imamichi","year":"2017","journal-title":"Sci Rep"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1210\/en.2006-0162","article-title":"Differentiation of adult stem cells derived from bone marrow stroma into Leydig or adrenocortical cells","volume":"147","author":"Yazawa","year":"2006","journal-title":"Endocrinology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/ani13040622","article-title":"Comparison of placental HSD17B1 expression and its regulation in various mammalian species","volume":"13","author":"Yazawa","year":"2023","journal-title":"Animals: an Open Access J MDPI"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2021.657360","article-title":"Profiles of 5\u03b1-reduced androgens in humans and eels: 5\u03b1-dihydrotestosterone and 11-ketodihydrotestosterone are active androgens produced in eel gonads","volume":"12","author":"Yazawa","year":"2021","journal-title":"Front Endocrinol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2021.105847","article-title":"11-Ketotestosterone is a major androgen produced in porcine adrenal glands and testes","volume":"210","author":"Yazawa","year":"2021","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B25","doi-asserted-by":"publisher","first-page":"18","DOI":"10.1530\/edm-18-0108","article-title":"A rare variety of congenital adrenal hyperplasia with mosaic Klinefelter syndrome: a unique combination presenting with ambiguous genitalia and sexual precocity","volume":"2018","author":"Shehab","year":"2018","journal-title":"Endocrinology Diabetes Metab Case Rep"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.3390\/jcm11195767","article-title":"Genetic testing for a patient with suspected 3 beta-hydroxysteroid dehydrogenase deficiency: A case of unreported genetic variants","volume":"11","author":"Menegatti","year":"2022","journal-title":"J Clin Med"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.17219\/acem\/131220","article-title":"Three cases of 3\u03b2-hydroxysteroid dehydrogenase deficiency: Clinical analysis","volume":"30","author":"Chen","year":"2021","journal-title":"Adv Clin Exp medicine: Off Organ Wroclaw Med Univ"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1210\/js.2018-00082","article-title":"Extensive bilateral adrenal rest testicular tumors in a patient with 3\u03b2-hydroxysteroid dehydrogenase type 2 deficiency","volume":"2","author":"Lolis","year":"2018","journal-title":"J Endocrine Soc"},{"key":"B29","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.jsbmb.2015.11.005","article-title":"Development of a novel cell based androgen screening model","volume":"156","author":"Campana","year":"2016","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1016\/j.cca.2017.05.002","article-title":"Reference intervals for plasma concentrations of adrenal steroids measured by LC-MS\/MS: Impact of gender, age, oral contraceptives, body mass index and blood pressure status","volume":"470","author":"Eisenhofer","year":"2017","journal-title":"Clinica chimica acta; Int J Clin Chem"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6874-9-10","article-title":"Dietary fat intake and gestational weight gain in relation to estradiol and progesterone plasma levels during pregnancy: a longitudinal study in Swedish women","volume":"9","author":"Lof","year":"2009","journal-title":"BMC women\u2019s Health"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1007\/s43032-021-00834-6","article-title":"Circulating innate lymphoid cells exhibit distinctive distribution during normal pregnancy","volume":"29","author":"Zhao","year":"2022","journal-title":"Reprod Sci (Thousand Oaks Calif.)"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2008-2257","article-title":"Patterns of plasma corticotropin-releasing hormone, progesterone, estradiol, and estriol change and the onset of human labor","volume":"94","author":"Smith","year":"2009","journal-title":"J Clin Endocrinol Metab"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27103164","article-title":"Biotransformation of phytosterols into androstenedione-A technological prospecting study","volume":"27","author":"Nunes","year":"2022","journal-title":"Molecules (Basel Switzerland)"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1007\/s42000-022-00385-8","article-title":"The effect of androstenedione supplementation on testosterone, estradiol, body composition, and lipid profile: a systematic review and meta-analysis of randomized controlled trials","volume":"21","author":"Pang","year":"2022","journal-title":"Hormones (Athens Greece)"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsbmb.2023.106403","article-title":"Serum steroid metabolite profiling by LC-MS\/MS in two phenotypic male patients with HSD17B3 deficiency: Implications for hormonal diagnosis","volume":"234","author":"Fujisawa","year":"2023","journal-title":"J Steroid Biochem Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.3390\/ijms231710026","article-title":"Disorder of sex development due to 17-beta-hydroxysteroid dehydrogenase type 3 deficiency: A case report and review of 70 different HSD17B3 mutations reported in 239 patients","volume":"23","author":"Gon\u00e7alves","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1210\/jendso\/bvaa192","article-title":"11-oxygenated androgens useful in the setting of discrepant conventional biomarkers in 21-hydroxylase deficiency","volume":"5","author":"Jha","year":"2021","journal-title":"J Endocrine Soc"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.834549","article-title":"Molecular diagnosis of steroid 21-hydroxylase deficiency: A practical approach","volume":"13","author":"Arriba","year":"2022","journal-title":"Front Endocrinol"},{"key":"B40","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1007\/s42000-018-0013-9","article-title":"5-\u03b1-Reductase type 2 deficiency: is there a genotype-phenotype correlation? A review","volume":"17","author":"Avenda\u00f1o","year":"2018","journal-title":"Hormones (Athens Greece)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1159\/000525119","article-title":"The molecular basis of 5\u03b1-reductase type 2 deficiency","volume":"16","author":"Batista","year":"2022","journal-title":"Sexual development: genetics Mol biology evolution endocrinology embryology Pathol sex determination differentiation"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-2311","article-title":"11-ketotestosterone is a major androgen produced in human gonads","volume":"101","author":"Imamichi","year":"2016","journal-title":"J Clin Endocrinol Metab"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)98548-0","article-title":"Characterization of the structure-activity relationships of rat types I and II 3 beta-hydroxysteroid dehydrogenase\/delta 5 -delta 4 isomerase by site-directed mutagenesis and expression in HeLa cells","volume":"266","author":"Simard","year":"1991","journal-title":"J Biol Chem"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.84.12.6288","article-title":"New insight into the molecular basis of 3beta-hydroxysteroid dehydrogenase deficiency: identification of eight mutations in the HSD3B2 gene eleven patients from seven new families and comparison of the functional properties of twenty-five mutant enzymes","volume":"84","author":"Moisan","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1210\/jcem.85.5.6581","article-title":"A novel A10E homozygous mutation in the HSD3B2 gene causing severe salt-wasting 3beta-hydroxysteroid dehydrogenase deficiency in 46,XX and 46,XY French-Canadians: evaluation of gonadal function after puberty","volume":"85","author":"Alos","year":"2000","journal-title":"J Clin Endocrinol Metab"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgaa022","article-title":"Revisiting classical 3\u03b2-hydroxysteroid dehydrogenase 2 deficiency: lessons from 31 pediatric cases","volume":"105","author":"Guran","year":"2020","journal-title":"J Clin Endocrinol Metab"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1021\/bi00009a020","article-title":"Identification and characterization of the G15D mutation found in a male patient with 3 beta-hydroxysteroid dehydrogenase (3 beta-HSD) deficiency: alteration of the putative NAD-binding domain of type II 3 beta-HSD","volume":"34","author":"Rh\u00e9aume","year":"1995","journal-title":"Biochemistry"},{"key":"B48","article-title":"Congenital adrenal hyperplasia due to 3 beta-hydroxysteroid dehydrogenase type II deficiency in 4 Saudi children. Long term follow up","volume":"25","author":"Bin-Abbas","year":"2004","journal-title":"Saudi Med J"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.3389\/fendo.2022.867073","article-title":"Genotype, mortality, morbidity, and outcomes of 3\u03b2-hydroxysteroid dehydrogenase deficiency in Algeria","volume":"13","author":"Ladjouze","year":"2022","journal-title":"Front Endocrinol"},{"key":"B50","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1530\/ec-17-0306","article-title":"Human 3beta-hydroxysteroid dehydrogenase deficiency associated with normal spermatic numeration despite a severe enzyme deficit","volume":"7","author":"Donadille","year":"2018","journal-title":"Endocrine connections"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1038\/ng0792-239","article-title":"Congenital adrenal hyperplasia due to point mutations in the type II 3 beta-hydroxysteroid dehydrogenase gene","volume":"1","author":"Rh\u00e9aume","year":"1992","journal-title":"Nat Genet"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.1159\/000185492","article-title":"Pubertal changes in testicular 3 beta-hydroxysteroid dehydrogenase activity in a male with classical 3 beta-hydroxysteroid dehydrogenase deficiency showing spontaneous secondary sexual maturation","volume":"48","author":"Yoshimoto","year":"1997","journal-title":"Hormone Res"},{"key":"B53","doi-asserted-by":"publisher","first-page":"K1","DOI":"10.1530\/eje-15-0599","article-title":"Human 3\u03b2-hydroxysteroid dehydrogenase deficiency seems to affect fertility but may not harbor a tumor risk: lesson from an experiment of nature","volume":"173","author":"Burckhardt","year":"2015","journal-title":"Eur J Endocrinol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1677\/jme-10-0006","article-title":"ACTH is a potent regulator of gene expression in human adrenal cells","volume":"45","author":"Xing","year":"2010","journal-title":"J Mol Endocrinol"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1480722\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,2]],"date-time":"2024-10-02T00:31:24Z","timestamp":1727829084000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2024.1480722\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,2]]},"references-count":54,"alternative-id":["10.3389\/fendo.2024.1480722"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2024.1480722","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,2]]},"article-number":"1480722"}}