{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T06:44:27Z","timestamp":1790837067997,"version":"4.1.0"},"reference-count":49,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2012,2,9]],"date-time":"2012-02-09T00:00:00Z","timestamp":1328745600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2012,5]]},"abstract":"<jats:p>\n                    Fetal growth restriction associates with increased risk of adult cardiometabolic and neuropsychiatric disorders. Both maternal malnutrition [notably a low\u2010protein (LP) diet] and stress\/glucocorticoid exposure reduce fetal growth and cause persisting abnormalities (programming) in adult offspring. Deficiency of placental 11 \u03b2\u2010hydroxysteroid dehydrogenase\u20102 (\n                    <jats:italic>11\u03b2\u2010HSD2<\/jats:italic>\n                    ), which inactivates glucocorticoids, is reduced by an LP diet and has been proposed as a unifying mechanism. Here, we explored the importance of glucocorticoids and placental\n                    <jats:italic>11\u03b2\u2010HSD2<\/jats:italic>\n                    in dietary programming. Pregnant mice were fed a control or isocaloric LP diet throughout gestation. The LP diet first elevated fetal glucocorticoid levels, then reduced placental growth, and finally decreased fetal weight near term by 17%. Whereas the LP diet reduced placental\n                    <jats:italic>11\u03b2\u2010HSD2<\/jats:italic>\n                    activity near term by ~25%, consistent with previous reports, activity was increased between 20 and 40% at earlier ages, implying that glucocorticoid overexposure in LP fetuses occurs\n                    <jats:italic>via 11\u03b2\u2010HSD2\u2010<\/jats:italic>\n                    independent mechanisms. Consistent with this, heterozygous\n                    <jats:italic>11<\/jats:italic>\n                    \u03b2\n                    <jats:italic>\u2010HSD2<\/jats:italic>\n                    <jats:sup>+\/\u2010<\/jats:sup>\n                    crosses showed that although both LP and 11\u03b2\u2010HSD2 deficiency reduced fetal growth, LP indeed acted independently of 11\u03b2\u2010HSD2. Instead, the LP diet induced the fetal hypothalamic\u2010pituitary\u2010adrenal axis\n                    <jats:italic>per se.<\/jats:italic>\n                    Thus, maternal malnutrition and placental\n                    <jats:italic>11\u03b2\u2010HSD2<\/jats:italic>\n                    deficiency act\n                    <jats:italic>via<\/jats:italic>\n                    distinct processes to retard fetal growth, both involving fetoplacental overexposure to glucocorticoids but from distinct sources.\u2014Cottrell, E. C., Holmes, M. C., Livingstone, D. E., Keynon, C. J., Seckl, J. R. Reconciling the nutritional and glucocorticoid hypotheses of fetal programming.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    26, 1866\u20101874 (2012).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.12-203489","type":"journal-article","created":{"date-parts":[[2012,2,10]],"date-time":"2012-02-10T01:03:04Z","timestamp":1328835784000},"page":"1866-1874","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":87,"title":["Reconciling the nutritional and glucocorticoid hypotheses of fetal programming"],"prefix":"10.1096","volume":"26","author":[{"given":"Elizabeth C.","family":"Cottrell","sequence":"first","affiliation":[{"name":"Endocrinology Unit Centre for Cardiovascular Science Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Megan C.","family":"Holmes","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Centre for Cardiovascular Science Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dawn E.","family":"Livingstone","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Centre for Cardiovascular Science Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Kenyon","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Centre for Cardiovascular Science Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan R.","family":"Seckl","sequence":"additional","affiliation":[{"name":"Endocrinology Unit Centre for Cardiovascular Science Queen's Medical Research Institute University of Edinburgh Edinburgh UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,2,9]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/07315724.2004.10719428"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)91224-A"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7610.2006.01714.x"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/neuro.08.019.2009"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1530\/jrf.0.0990283"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(05)60824-0"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(93)90148-A"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1460-9568.2000.00958.x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s001250050573"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020970"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0039-128X(96)00033-5"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI1567"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4464-05.2006"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.83.7.2244"},{"key":"e_1_2_7_16_1","first-page":"1660","article-title":"Reduced 11 \u03b2\u2010hydroxysteroid dehydrogenase type 2 activity is associated with decreased birth weight centile in pregnancies complicated by asthma","volume":"87","author":"Murphy V. E.","year":"2002","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.3.885"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4004(96)80010-5"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.5.8139"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.142.7.2854"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyh083"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2011.03.001"},{"key":"e_1_2_7_23_1","doi-asserted-by":"crossref","first-page":"2841","DOI":"10.1210\/endo.142.7.8238","article-title":"The maternal diet during pregnancy programs altered expression of the glucocorticoid receptor and type 2 11 \u03b2\u2010hydroxysteroid dehydrogenase: potential molecular mechanisms underlying the programming of hypertension in utero","volume":"142","author":"Bertram C.","year":"2001","journal-title":"Endocrinology"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1097\/00004872-199715050-00010"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.2337\/db07-1530"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.1.7887"},{"key":"e_1_2_7_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M402822200"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2826.1990.tb00659.x"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(97)04000-8"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2005.01.001"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2265.1997.1230939.x"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2008-1100"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.181214"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.80.9.2700"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0739-7240(01)00107-2"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0303-7207(01)00629-3"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.placenta.2009.11.016"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0504468103"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.156133"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-0189"},{"key":"e_1_2_7_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1080803"},{"key":"e_1_2_7_42_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00574.2006"},{"key":"e_1_2_7_43_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.2001.281.6.R1966"},{"key":"e_1_2_7_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsgi.2005.02.003"},{"key":"e_1_2_7_45_1","doi-asserted-by":"publisher","DOI":"10.1095\/biolreprod60.3.541"},{"key":"e_1_2_7_46_1","doi-asserted-by":"publisher","DOI":"10.1210\/en.2009-0479"},{"key":"e_1_2_7_47_1","doi-asserted-by":"publisher","DOI":"10.1067\/mob.2003.62"},{"key":"e_1_2_7_48_1","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2004-0113"},{"key":"e_1_2_7_49_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejogrb.2011.01.008"},{"key":"e_1_2_7_50_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2009.173013"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.12-203489","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.12-203489","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.12-203489","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,28]],"date-time":"2025-10-28T19:59:42Z","timestamp":1761681582000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.12-203489"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,2,9]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2012,5]]}},"alternative-id":["10.1096\/fj.12-203489"],"URL":"https:\/\/doi.org\/10.1096\/fj.12-203489","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,2,9]]},"assertion":[{"value":"2012-01-06","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-01-30","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-02-09","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}