{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T04:51:15Z","timestamp":1789707075312,"version":"4.0.1"},"reference-count":47,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Clinical Endocrinology"],"published-print":{"date-parts":[[2025,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Introduction<\/jats:title><jats:p>Premature adrenarche (PremA), is associated with increased adiposity and in girls to earlier puberty and adverse metabolic profiles. Recently LC\u2010MS\/MS studies demonstrated adrenal production of more potent androgens: 11\u2010oxygenated C19 steroids. Defining the mechanisms that regulate adrenal 11\u2010oxygenated C19 steroids production has been elusive. We recently showed that genetic determinants of DHEAS during adrenarche differed from those during adulthood. One highly significant variant was at the prolactin receptor which is strongly expressed in human adrenal tissue. The aim of this study is to test whether an association exists between DHEAS\/11\u2010oxygenated C19 steroids and prolactin concentrations in pre\u2010pubertal girls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Two hundred and forty four prepubertal girls recruited within the \u2018the Food and Environment Chilean Cohort,\u2019 with normal birth weight (3.37\u2009\u00b1\u20090.02 Kg) were examined at 6.7\u2009\u00b1\u20090.6 years, including anthropometry and blood sampling. DHEAS and 11\u2010oxygenated C19 steroids were measured by LC\u2010MS\/MS. Girls were categorized according to the DHEAS concentrations in normal DHEAS (ND, &lt;\u200975th percentile for the population) or high DHEAS (HD, \u2265\u200975th percentile). This definition of adrenarche subgroups allows identification of PremA independently from other factors influencing clinical manifestations (i.e ethnicity, tissue sensitivity).<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>None of the girls presented clinical evidence of pubarche. At this age mean DHEAS concentration was 16.4 (9.6, \u221225) \u03bcg\/dL and the 75th percentile set at 25.0\u2009\u03bcg\/dL. Girls with HD had higher weight (1.3\u2009\u00b1\u20091.2 vs. 0.7\u2009\u00b1\u20091.1, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), height (0.6\u2009\u00b1\u20091.0 vs. 0\u2009\u00b1\u20090.9, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) and BMI (1.3\u2009\u00b1\u20091.2 vs. 0.9\u2009\u00b1\u20091.1, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01) SDs compared to ND. The concentrations of all 11\u2010oxygenated C19 steroids (ng\/mL) were higher in girls with HD compared to girls with ND: 11KA by 16% [0.14 (0.12, 0.16) vs. 0.12 (0.10, 0.14)], 11OHA by 43% [0.07 (0.05, 0.08) vs. 0.04 (0.03, 0.05)], 11KT by 35% [0.19(0.15, 0.25) vs. 0.14 (0.11, 0.19)] and 11OHT by 30% [0.03 (0.02, 0.05) vs. 0.03 (0.01, 0.04)]. DHEAS levels correlated with each of the 11\u2010oxygenated C19 steroids both in the raw and in fully adjusted model. Prolactin levels [6.5 (4.4, 10.7) vs. 5.7 (4.1, 9.3)] ng\/mL and insulin [7.2 (5.7, 8.7) vs. 6.8 (5.3, \u22129.4)] \u03bcUI\/mL did not differ in HD compared to ND girls. Prolactin levels were not associated with DHEAS concentrations but significantly associated with 11KA (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) even after adjustment by covariates and was close to the limit of significance in the fully adjusted model for 11OHA (<jats:italic>p<\/jats:italic>\u2009=\u20090.051).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Our observations confirm that 11KT is the dominant bioactive androgen in children during adrenarche and PremA. Prolactin levels are directly correlated to the concentrations of the adrenal bioactive androgens. Conditions or medications that increase prolactin concentrations during childhood could have a role in PremA.<\/jats:p><\/jats:sec>","DOI":"10.1111\/cen.15227","type":"journal-article","created":{"date-parts":[[2025,3,8]],"date-time":"2025-03-08T20:22:48Z","timestamp":1741465368000},"page":"66-73","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Prolactin and Adrenal Androgens During Adrenarche"],"prefix":"10.1111","volume":"103","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9247-2982","authenticated-orcid":false,"given":"German","family":"I\u00f1iguez","sequence":"first","affiliation":[{"name":"Institute of Maternal and Child Research, Faculty of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esteban","family":"Barnafi","sequence":"additional","affiliation":[{"name":"BK Laboratories Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enzo","family":"Lalli","sequence":"additional","affiliation":[{"name":"Institut de Pharmacologie Mol\u00e9culaire et Cellulaire CNRS UMR7275 Valbonne France"},{"name":"Inserm U1323 Valbonne France"},{"name":"Universit\u00e9 C\u00f4te d'Azur Valbonne France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1587-4264","authenticated-orcid":false,"given":"Ana","family":"Pereira","sequence":"additional","affiliation":[{"name":"Institute of Nutrition and Food Technology University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pedro","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Institute of Nutrition and Food Technology University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2287-0181","authenticated-orcid":false,"given":"Ver\u00f3nica","family":"Mericq","sequence":"additional","affiliation":[{"name":"Institute of Maternal and Child Research, Faculty of Medicine University of Chile Santiago Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1210\/endrev\/bnab009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(00)00404-4"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.3945\/ajcn.112.037325"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2006-2412"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-15-1181"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2016-3285"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1530\/EJE-20-0129"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2012-2912"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mce.2013.07.006"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1002\/cphy.c140006"},{"issue":"12","key":"e_1_2_7_12_1","first-page":"4589","article-title":"11\u2010Ketotestosterone Is the Dominant Circulating Bioactive Androgen During Normal and Premature Adrenarche","volume":"103","author":"Rege J.","year":"2018","journal-title":"Journal of Clinical Endocrinology and Metabolism"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1210\/jcem-55-2-251"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/bies.202200109"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgab814"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2014-2049"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/pr.2014.21"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2013-1284"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12937-020-00583-3"},{"key":"e_1_2_7_20_1","volume-title":"Pobreza y Distribuci\u00f3n del Ingreso en la Regi\u00f3n Metropolitana de Santiago: Resultados Encuesta Casen 2015","author":"SEREMI de Desarrollo Social Metropolitana","year":"2016"},{"key":"e_1_2_7_21_1","unstructured":"Junta Nacional de Auxilio Escolar y Becas (JUNAEB) Departamento de Planificaci\u00f3n y Estudios Ministerio de Educaci\u00f3n.Informe Mapa Nutricional2016 https:\/\/www.junaeb.cl\/wp-content\/uploads\/2023\/03\/Presentacion-resultados-MN-2016.pdf."},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1186\/1472-6874-14-96"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1159\/000506632"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1159\/000513236"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201701274RR"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.1580969.x"},{"issue":"1","key":"e_1_2_7_27_1","first-page":"34","article-title":"Cortisol Production Rate. 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