title: Prenatal dexamethasone exposure potentiates diet-induced hepatosteatosis and decreases plasma IGF-I in a sex-specific fashion.
abstract: The clinical use of synthetic glucocorticoids in preterm infants to promote lung development has received considerable attention due to the potential for increased risk of developing metabolic disease in adulthood after such treatment. In this study, we examined the hypothesis that exposure to the synthetic glucocorticoid, dexamethasone (DEX), during late gestation in the rat results in the development of nonalcoholic fatty liver disease in adult offspring. Pregnant Sprague Dawley dams were treated with 0.4 mg/kg DEX beginning on gestational d 18 until parturition (gestational d 23). At postnatal d 21, offspring were weaned onto either a standard chow or high-fat (60% fat-derived calories) diet. In adulthood (postnatal d 60-65), hepatic tissue was harvested and examined for pathology. Liver steatosis, or fat accumulation, was found to be more severe in the DEX-exposed female offspring that were weaned onto the high-fat diet. This finding corresponded with decreased plasma IGF-I concentrations, as well as decreased hypothalamic expression of GHRH mRNA. Morphological measurements on body and long bone length further implicate a GH signaling deficit after fetal DEX exposure. Collectively, these data indicate suppression of GH axis function in the female DEX/high-fat cohort but not in the male offspring. Because deficits in the GH signaling can be linked to the development of nonalcoholic fatty liver disease, our results suggest that the prominent liver injury noted in female offspring exposed to DEX during late gestation may stem from abnormal development of the GH axis at the hypothalamic level.
authors: Department of Basic Medical Sciences, University of Arizona College of Medicine-Phoenix, 425 North 5th Street, Phoenix, Arizona 85004, USA. carbone@email.arizona.edu
authors: David L
authors: DL
authors: Carbone
authors: Damian G
authors: DG
authors: Zuloaga
authors: Ryoko
authors: R
authors: Hiroi
authors: Chad D
authors: CD
authors: Foradori
authors: Marie E
authors: ME
authors: Legare
authors: Robert J
authors: RJ
authors: Handa
mesh_terms: D000818:Animals; D001483:Base Sequence; D001846:Bone Development / Q000187:drug effects; D003907:Dexamethasone / Q000008:administration & dosage* / Q000633:toxicity*; D059305:Diet, High-Fat / Q000009:adverse effects; D005234:Fatty Liver / Q000097:blood / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D005260:Female; D005865:Gestational Age; D013006:Growth Hormone / Q000378:metabolism; D006801:Humans; D007031:Hypothalamus / Q000187:drug effects / Q000196:embryology / Q000378:metabolism; D007231:Infant, Newborn; D007334:Insulin-Like Growth Factor I / Q000378:metabolism*; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000097:blood / Q000209:etiology / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012727:Sex Characteristics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I; D003907:Dexamethasone; D013006:Growth Hormone