Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
| Autor: | Peter W. Nathanielsz, Guadalupe L. Rodríguez-González, Florian Rakers, Martin Schmidt, Marius Nistor, René Schiffner, Teodora Daneva, Matthias Schwab, Thomas Lehmann |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Blood Glucose Hydrocortisone Swine Pituitary-Adrenal System Dexamethasone HPA axis ACTH cortisol stress response hypoglycemia lcsh:Chemistry 0302 clinical medicine Pregnancy lcsh:QH301-705.5 Spectroscopy General Medicine Computer Science Applications Maternal Exposure Prenatal Exposure Delayed Effects Gestation Female Glucocorticoid medicine.drug medicine.medical_specialty Hypothalamo-Hypophyseal System Hypoglycemia Catalysis Article Inorganic Chemistry 03 medical and health sciences Stress Physiological Diabetes mellitus Internal medicine medicine Animals Physical and Theoretical Chemistry Molecular Biology Fetus business.industry Organic Chemistry medicine.disease 030104 developmental biology Endocrinology Blood pressure lcsh:Biology (General) lcsh:QD1-999 business 030217 neurology & neurosurgery |
| Zdroj: | International Journal of Molecular Sciences; Volume 18; Issue 11; Pages: 2241 International Journal of Molecular Sciences International Journal of Molecular Sciences, Vol 18, Iss 11, p 2241 (2017) |
| ISSN: | 1422-0067 |
| DOI: | 10.3390/ijms18112241 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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