Cargando…

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

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. Activatio...

Descripción completa

Detalles Bibliográficos
Autores principales: Schiffner, René, Rodríguez-González, Guadalupe L., Rakers, Florian, Nistor, Marius, Nathanielsz, Peter W., Daneva, Teodora, Schwab, Matthias, Lehmann, Thomas, Schmidt, Martin
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2017
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713211/
https://www.ncbi.nlm.nih.gov/pubmed/29077038
http://dx.doi.org/10.3390/ijms18112241
_version_ 1783283370463068160
author Schiffner, René
Rodríguez-González, Guadalupe L.
Rakers, Florian
Nistor, Marius
Nathanielsz, Peter W.
Daneva, Teodora
Schwab, Matthias
Lehmann, Thomas
Schmidt, Martin
author_facet Schiffner, René
Rodríguez-González, Guadalupe L.
Rakers, Florian
Nistor, Marius
Nathanielsz, Peter W.
Daneva, Teodora
Schwab, Matthias
Lehmann, Thomas
Schmidt, Martin
author_sort Schiffner, René
collection PubMed
description 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.
format Online
Article
Text
id pubmed-5713211
institution National Center for Biotechnology Information
language English
publishDate 2017
publisher MDPI
record_format MEDLINE/PubMed
spelling pubmed-57132112017-12-07 Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs Schiffner, René Rodríguez-González, Guadalupe L. Rakers, Florian Nistor, Marius Nathanielsz, Peter W. Daneva, Teodora Schwab, Matthias Lehmann, Thomas Schmidt, Martin Int J Mol Sci Article 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. MDPI 2017-10-27 /pmc/articles/PMC5713211/ /pubmed/29077038 http://dx.doi.org/10.3390/ijms18112241 Text en © 2017 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Schiffner, René
Rodríguez-González, Guadalupe L.
Rakers, Florian
Nistor, Marius
Nathanielsz, Peter W.
Daneva, Teodora
Schwab, Matthias
Lehmann, Thomas
Schmidt, Martin
Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title_full Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title_fullStr Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title_full_unstemmed Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title_short Effects of Late Gestational Fetal Exposure to Dexamethasone Administration on the Postnatal Hypothalamus-Pituitary-Adrenal Axis Response to Hypoglycemia in Pigs
title_sort effects of late gestational fetal exposure to dexamethasone administration on the postnatal hypothalamus-pituitary-adrenal axis response to hypoglycemia in pigs
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5713211/
https://www.ncbi.nlm.nih.gov/pubmed/29077038
http://dx.doi.org/10.3390/ijms18112241
work_keys_str_mv AT schiffnerrene effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT rodriguezgonzalezguadalupel effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT rakersflorian effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT nistormarius effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT nathanielszpeterw effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT danevateodora effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT schwabmatthias effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT lehmannthomas effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs
AT schmidtmartin effectsoflategestationalfetalexposuretodexamethasoneadministrationonthepostnatalhypothalamuspituitaryadrenalaxisresponsetohypoglycemiainpigs