Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
Open Access
- 27 October 2017
- journal article
- research article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 18 (11), 2241
- https://doi.org/10.3390/ijms18112241
Abstract
Background: Prenatal glucocorticoid administration alters the activity of the fetal hypothalamic-pituitary-adrenocortical axis (HPAA), and correspondingly the adenocorticotropic hormone (ACTH) and cortisol levels after birth. The dosages required for these effects are critically discussed. Activation of the HPAA is related to metabolic syndrome and diabetes mellitus. Hypoglycemia is the classic side effect of antidiabetic treatment. We hypothesized that a low dosage of dexamethasone in late pregnancy alters the HPAA response to hypoglycemia in pigs. Methods: 12 pregnant sows were randomly assigned to two groups which received either a low-dose intramuscular injection (99th and 100th day of gestation) of dexamethasone (0.06 μg/kg body weight) or vehicle. Three months after birth, 18 dexamethasone-treated anaesthetized offspring and 12 control offspring underwent a 75 min hypoglycemic clamp (blood glucose below 4 mmol/L) procedure. Heart rate (HR), blood pressure, ACTH and cortisol levels and body weight (at birth and after three months) were recorded. Results: Dexamethasone-treated animals exhibited significantly elevated ACTH (139.9 ± 12.7 pg/mL) and cortisol (483.1 ± 30.3 nmol/L) levels during hypoglycemia as compared to the control group (41.7 ± 6.5 pg/mL and 257.9 ± 26.7 nmol/L, respectively), as well as an elevated HR (205.5 ± 5.7 bpm) and blood pressure (systolic: 128.6 ± 1.5, diastolic: 85.7 ± 0.7 mmHg) response as compared to the control group (153.2 ± 4.5 bpm; systolic: 118.6 ± 1.6, diastolic: 79.5 ± 1.4 mmHg, respectively; p < 0.001). Conclusions: Low-dose prenatal administration of dexamethasone not only exerts effects on the HPAA (ACTH and cortisol concentration) and vital parameters (HR and diastolic blood pressure) under baseline conditions, but also on ACTH, HR and systolic blood pressure during hypoglycemia.This publication has 42 references indexed in Scilit:
- Australasian randomised trial to evaluate the role of maternal intramuscular dexamethasone versus betamethasone prior to preterm birth to increase survival free of childhood neurosensory disability (A*STEROID): study protocolBMC Pregnancy and Childbirth, 2013
- Effects of antenatal corticosteroids on the hypothalamic-pituitary-adrenocortical axis of the fetus and newborn: experimental findings and clinical considerationsAmerican Journal of Obstetrics and Gynecology, 2012
- Obesity and adipokines: effects on sympathetic overactivityJournal Of Physiology-London, 2012
- Repeated antenatal corticosteroid treatment: a systematic review and meta-analysisActa Obstetricia et Gynecologica Scandinavica, 2011
- Sympathetic nervous activation in obesity and the metabolic syndrome—Causes, consequences and therapeutic implicationsPharmacology & Therapeutics, 2010
- Review and meta-analysis: Benefits and risks of multiple courses of antenatal corticosteroidsThe Journal of Maternal-Fetal & Neonatal Medicine, 2010
- Glucocorticoid Signaling in the CellAnnals of the New York Academy of Sciences, 2009
- Review and meta-analysis: Benefits and risks of multiple courses of antenatal corticosteroidsThe Journal of Maternal-Fetal & Neonatal Medicine, 2009
- Long-Term Outcomes after Repeat Doses of Antenatal CorticosteroidsThe New England Journal of Medicine, 2007
- Cortisol and catecholamines changes as functions of time-of-day and self-reported moodNeuroscience & Biobehavioral Reviews, 1985