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Int. J. Mol. Sci. 2017, 18(11), 2241; https://doi.org/10.3390/ijms18112241

Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs

1
Department of Neurology, Jena University Hospital—Friedrich Schiller University, 07747 Jena, Germany
2
Orthopaedic Department, Jena University Hospital—Friedrich Schiller University, 07747 Jena, Germany
3
Reproductive Biology, National Institute of Medical Science and Nutrition, 14000 Mexico City, Mexico
4
Department of Animal Science, University of Wyoming, Laramie, 82071 WY, USA
5
Institute of Biology and Immunology of Reproduction, Bulgarian Academy of Sciences, 1113 Sofia, Bulgaria
6
Institute of Medical Statistics, Computer Sciences and Documentation Science, Jena University Hospital—Friedrich Schiller University, 07743 Jena, Germany
7
Institute for Biochemistry II, Jena University Hospital—Friedrich Schiller University, 07743 Jena, Germany
*
Author to whom correspondence should be addressed.
Received: 24 September 2017 / Revised: 19 October 2017 / Accepted: 21 October 2017 / Published: 27 October 2017
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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. View Full-Text
Keywords: HPA axis; ACTH; cortisol; stress response; hypoglycemia HPA axis; ACTH; cortisol; stress response; hypoglycemia
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Schiffner, R.; Rodríguez-González, G.L.; Rakers, F.; Nistor, M.; Nathanielsz, P.W.; Daneva, T.; Schwab, M.; Lehmann, T.; Schmidt, M. Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs. Int. J. Mol. Sci. 2017, 18, 2241.

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