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https://hdl.handle.net/2440/61846
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Type: | Journal article |
Title: | Sex-specific associations between cortisol and birth weight in pregnancies complicated by asthma are not due to differential glucocorticoid receptor expression |
Author: | Hodyl, N. Wyper, H. Osei-Kumah, A. Scott, N. Murphy, V. Gibson, P. Smith, R. Clifton, V. |
Citation: | Thorax, 2010; 65(8):677-683 |
Publisher: | British Med Journal Publ Group |
Issue Date: | 2010 |
ISSN: | 0040-6376 1468-3296 |
Statement of Responsibility: | Nicolette A Hodyl, Hayley Wyper, Annette Osei-Kumah, Naomi Scott, Vanessa E Murphy, Peter Gibson, Roger Smith and Vicki L Clifton |
Abstract: | Background: Fetal growth inhibition is a known sequelae of in utero glucocorticoid exposure and has long-term consequences for adult health. Sex-specific fetal growth patterns are observed in pregnancies with maternal asthma and may be due to differential sensitivity of the placenta to glucocorticoids. It is currently unknown whether expression of the placental glucocorticoid receptor (GR) becomes altered with asthma or the use of inhaled corticosteroids. Methods: Pregnant women with mild asthma (n¼52), moderate-severe asthma (n¼71) and without asthma (n¼51) were recruited at John Hunter Hospital, Newcastle, Australia. At delivery, placentae and cord blood were collected, and fetal sex and birth weight were recorded. Placental GR heterogeneous nuclear RNA (hnRNA), mRNA and protein were measured and cord blood cortisol concentrations were assessed. Results Placental GR gene activity increased with cortisol exposure but decreased with inhaled corticosteroid treatment (p¼0.05). With maternal asthma, female birth weight centiles were inversely associated with cortisol (r¼_0.286, p¼0.017) and, despite a decrease in placental GR mRNA (p¼0.003), placental GRa protein levels were unchanged. In males, no change to cortisol, birth weight or placental GR were evident in pregnancies with asthma. Together, these results indicate that in pregnancies complicated by asthma, placental GR gene activity, but not mRNA expression or protein levels, is dependent on cortisol and inhaled corticosteroid treatment. Conclusions The sex-specific associations between cortisol and birth weight observed in pregnancies with asthma are not due to altered GR expression; however, they may be due to differential glucocorticoid sensitivity via preferential transcription of GR isoforms or posttranslational modifications. |
Keywords: | Fetal Blood Placenta Humans Asthma Pregnancy Complications Birth Weight Hydrocortisone Receptors, Glucocorticoid RNA, Messenger Glucocorticoids Cohort Studies Reverse Transcriptase Polymerase Chain Reaction Smoking Sex Factors Gene Expression Regulation Fetal Development Pregnancy Maternal-Fetal Exchange Adult Female Male Young Adult |
Rights: | Copyright © The Authors |
DOI: | 10.1136/thx.2009.123091 |
Grant ID: | NHMRC |
Published version: | http://dx.doi.org/10.1136/thx.2009.123091 |
Appears in Collections: | Aurora harvest 5 Obstetrics and Gynaecology publications |
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hdl_61846.pdf | Published version | 288.23 kB | Adobe PDF | View/Open |
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