Cargando…
Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney
We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of d...
Autores principales: | , , , , , , , |
---|---|
Formato: | Texto |
Lenguaje: | English |
Publicado: |
American Physiological Society
2010
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825763/ https://www.ncbi.nlm.nih.gov/pubmed/19920212 http://dx.doi.org/10.1152/physiolgenomics.00088.2009 |
_version_ | 1782177834834329600 |
---|---|
author | Dunbar, Donald R. Khaled, Hiba Evans, Louise C. Al-Dujaili, Emad A. S. Mullins, Linda J. Mullins, John J. Kenyon, Christopher J. Bailey, Matthew A. |
author_facet | Dunbar, Donald R. Khaled, Hiba Evans, Louise C. Al-Dujaili, Emad A. S. Mullins, Linda J. Mullins, John J. Kenyon, Christopher J. Bailey, Matthew A. |
author_sort | Dunbar, Donald R. |
collection | PubMed |
description | We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of deoxycorticosterone, a weak mineralocorticoid, to levels of physiological significance. Nevertheless, we observed neither antinatriuresis nor kaliuresis in ACTH-treated mice, and plasma renin activity was not suppressed. We identified no changes in expression of mineralocorticoid target genes. Water turnover was increased in chronic ACTH-treated mice, as were hematocrit and hypertonicity: volume contraction is consistent with high levels of glucocorticoid. ACTH-treated mice exhibited other signs of glucocorticoid excess, such as enhanced weight gain and involution of the thymus. We identified novel ACTH-induced changes in 1) genes involved in vitamin D (Cyp27b1, Cyp24a1, Gc) and calcium (Sgk, Calb1, Trpv5) metabolism associated with calciuria and phosphaturia; 2) genes that would be predicted to desensitize the kidney to glucocorticoid action (Nr3c1, Hsd11b1, Fkbp5); and 3) genes encoding transporters of enzyme systems associated with xenobiotic metabolism and oxidative stress. Although there is evidence that ACTH-induced hypertension is a function of physiological cross talk between glucocorticoids and mineralocorticoids, the present study suggests that the major changes in electrolyte and fluid homeostasis and renal function are attributable to glucocorticoids. The calcium and organic anion metabolism pathways that are affected by ACTH may explain some of the known adverse effects associated with glucocorticoid excess. |
format | Text |
id | pubmed-2825763 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2010 |
publisher | American Physiological Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-28257632011-02-01 Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney Dunbar, Donald R. Khaled, Hiba Evans, Louise C. Al-Dujaili, Emad A. S. Mullins, Linda J. Mullins, John J. Kenyon, Christopher J. Bailey, Matthew A. Physiol Genomics Research Articles We investigated the effects on urinary steroid and electrolyte excretion and renal gene expression of chronic infusions of ACTH in the mouse. ACTH caused a sustained increase in corticosteroid excretion; aldosterone excretion was only transiently elevated. There was an increase in the excretion of deoxycorticosterone, a weak mineralocorticoid, to levels of physiological significance. Nevertheless, we observed neither antinatriuresis nor kaliuresis in ACTH-treated mice, and plasma renin activity was not suppressed. We identified no changes in expression of mineralocorticoid target genes. Water turnover was increased in chronic ACTH-treated mice, as were hematocrit and hypertonicity: volume contraction is consistent with high levels of glucocorticoid. ACTH-treated mice exhibited other signs of glucocorticoid excess, such as enhanced weight gain and involution of the thymus. We identified novel ACTH-induced changes in 1) genes involved in vitamin D (Cyp27b1, Cyp24a1, Gc) and calcium (Sgk, Calb1, Trpv5) metabolism associated with calciuria and phosphaturia; 2) genes that would be predicted to desensitize the kidney to glucocorticoid action (Nr3c1, Hsd11b1, Fkbp5); and 3) genes encoding transporters of enzyme systems associated with xenobiotic metabolism and oxidative stress. Although there is evidence that ACTH-induced hypertension is a function of physiological cross talk between glucocorticoids and mineralocorticoids, the present study suggests that the major changes in electrolyte and fluid homeostasis and renal function are attributable to glucocorticoids. The calcium and organic anion metabolism pathways that are affected by ACTH may explain some of the known adverse effects associated with glucocorticoid excess. American Physiological Society 2010-02 2009-11-17 /pmc/articles/PMC2825763/ /pubmed/19920212 http://dx.doi.org/10.1152/physiolgenomics.00088.2009 Text en Copyright © 2010 the American Physiological Society This document may be redistributed and reused, subject to www.the-aps.org/publications/journals/funding_addendum_policy.htm (http://www.the-aps.org/publications/journals/funding_addendum_policy.htm) . |
spellingShingle | Research Articles Dunbar, Donald R. Khaled, Hiba Evans, Louise C. Al-Dujaili, Emad A. S. Mullins, Linda J. Mullins, John J. Kenyon, Christopher J. Bailey, Matthew A. Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title | Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title_full | Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title_fullStr | Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title_full_unstemmed | Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title_short | Transcriptional and physiological responses to chronic ACTH treatment by the mouse kidney |
title_sort | transcriptional and physiological responses to chronic acth treatment by the mouse kidney |
topic | Research Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2825763/ https://www.ncbi.nlm.nih.gov/pubmed/19920212 http://dx.doi.org/10.1152/physiolgenomics.00088.2009 |
work_keys_str_mv | AT dunbardonaldr transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT khaledhiba transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT evanslouisec transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT aldujailiemadas transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT mullinslindaj transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT mullinsjohnj transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT kenyonchristopherj transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney AT baileymatthewa transcriptionalandphysiologicalresponsestochronicacthtreatmentbythemousekidney |