title: Adrenal steroidogenesis following prenatal dexamethasone exposure in the spiny mouse.
abstract: Antenatal stress disturbs the development of the fetal hypothalamic-pituitary-adrenal axis and adrenal steroidogenesis. We investigated the effect of brief maternal exposure to high glucocorticoids (dexamethasone (DEX)) at mid- and late-pregnancy on adrenal structure and production of steroids in spiny mouse. Pregnant spiny mice were treated for 60 h with 125 μg/kg DEX or saline s.c. by osmotic minipump at day 20 (0.5) or 30 (0.75) of gestation. Immunohistochemical expression of steroidogenic acute regulatory-protein (StAR), 3β-hydroxysteroid dehydrogenase (3βHSD), 17-hydroxylase,17-20lyase (P450C17), and cytochromeb5 (CYTB5) was determined in adrenals on postnatal (P) day 170±20. DHEA, testosterone, and cortisol were measured by RIA. Maternal DEX at 20 days significantly reduced the expression of STAR, P450C17 (CYP17A1), and CYTB5 in the adrenal zona reticularis (ZR) of adult offspring, with greater change in male vs female offspring (P<0.05). Plasma DHEA was decreased in male offspring from DEX-treated (6.84±1.24 ng/ml) vs saline-treated (13±0.06 ng/ml; P=0.01) dams, and the DHEA:cortisol ratio was lower in males (P<0.05). Testosterone levels increased in male offspring from DEX (266.03±50.75 pg/ml) vs saline (83.47±32.3 pg/ml, P<0.05)-treated dams. DEX treatment at 0.75 gestation had no significant effect on any parameters measured. This study shows that brief exposure to excess glucocorticoid has long-term impacts on the ZR and adrenal steroidogenesis, affecting the secretion of DHEA and testosterone in male offspring, an effect produced at 0.5 but not at 0.75 gestation. DHEA is important for brain development, and its suppression in adult life might contribute to the neurobehavioral pathologies that can arise after illness and stress during pregnancy.
authors.affiliation: Monash Institute of Medical Research, The Ritchie Centre, Monash University, 27-31 Wright Street, Clayton, Victoria 3168, Australia The Florey Institute of Neuroscience and Mental Health, University of Melbourne, Melbourne, Victoria 3010, Australia School of Biomedical Sciences, The University of Queensland, St Lucia, Queensland 4072, Australia Department of Obstetrics and Gynaecology, Monash Medical Centre, Monash University, Clayton, Victoria 3168, Australia.
authors.forename: Tracey A
authors.initials: TA
authors.lastname: Quinn
authors.forename: Udani
authors.initials: U
authors.lastname: Ratnayake
authors.forename: Margie
authors.initials: M
authors.lastname: Castillo-Melendez
authors.forename: Karen M
authors.initials: KM
authors.lastname: Moritz
authors.forename: Hayley
authors.initials: H
authors.lastname: Dickinson
authors.forename: David W
authors.initials: DW
authors.lastname: Walker
mesh_terms: D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000311:Adrenal Glands / Q000196:embryology / Q000254:growth & development / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D003907:Dexamethasone / Q000009:adverse effects*; D004622:Embryo, Mammalian; D005260:Female; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D005865:Gestational Age; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000378:metabolism* / Q000503:physiopathology
chemical_list: D000305:Adrenal Cortex Hormones; D003907:Dexamethasone
keywords: DHEA; P450C17; adrenal cortex; glucocorticoids; prenatal stress