{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,2]],"date-time":"2026-08-02T04:34:17Z","timestamp":1785645257197,"version":"3.56.0"},"reference-count":42,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T00:00:00Z","timestamp":1631145600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["17K10195"],"award-info":[{"award-number":["17K10195"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Low body weight at birth has been shown to be a risk factor for future metabolic disorders, as well as stress response abnormalities and depression. We showed that low-birthweight rats had prolonged high blood corticosterone levels after stress exposure, and that an increase in Gas5 lncRNA, a decoy receptor for glucocorticoid receptors (GRs), reduces glucocorticoid responsiveness. Thus, we concluded that dampened pituitary glucocorticoid responsiveness disturbed the glucocorticoid feedback loop in low-birthweight rats. However, it remains unclear whether such glucocorticoid responsiveness is suppressed solely in the pituitary or systemically. The expression of Gas5 lncRNA increased only in the pituitary, and the intact induction of expression of the GR co-chaperone factor Fkbp5 against dexamethasone was seen in the liver, muscle, and adipose tissue. Intervention with a methyl-modulator diet (folate, VB12, choline, betaine, and zinc) immediately before or one week after delivery reversed the expression level of Gas5 lncRNA in the pituitary of the offspring. Consequently, it partially normalized the blood corticosterone levels after restraint stress exposure. In conclusion, the mode of glucocorticoid response in low-birthweight rats is impaired solely in the pituitary, and intervention with methyl-modulators ameliorates the impairment, but with a narrow therapeutic time window.<\/jats:p>","DOI":"10.3390\/ijms22189767","type":"journal-article","created":{"date-parts":[[2021,9,9]],"date-time":"2021-09-09T12:20:37Z","timestamp":1631190037000},"page":"9767","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prenatal and Postnatal Methyl-Modulator Intervention Corrects the Stress-Induced Glucocorticoid Response in Low-Birthweight Rats"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0100-8763","authenticated-orcid":false,"given":"Takahiro","family":"Nemoto","sequence":"first","affiliation":[{"name":"Department of Bioregulatory Science (Physiology), Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5470-9128","authenticated-orcid":false,"given":"Yoshihiko","family":"Kakinuma","sequence":"additional","affiliation":[{"name":"Department of Bioregulatory Science (Physiology), Nippon Medical School, Tokyo 113-8602, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,9,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1136\/heart.84.6.595","article-title":"Coronary heart disease after prenatal exposure to the Dutch famine, 1944\u201345","volume":"84","author":"Roseboom","year":"2000","journal-title":"Heart"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16757","DOI":"10.1073\/pnas.1012911107","article-title":"The Dutch Hunger Winter and the developmental origins of health and disease","volume":"107","author":"Schulz","year":"2010","journal-title":"Proc. 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