Document Detail


Effects of cortisol on cardiac myocytes and on expression of cardiac genes in fetal sheep.
MedLine Citation:
PMID:  15576665     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In 17 fetal sheep aged 129 days, the effects of large-dose infusions of cortisol (72.1 mg/day for 2-3 days) on proliferation, binucleation, and hypertrophy of cardiac myocytes, cardiac expression of angiotensinogen, angiotensin receptor subtypes 1 and 2, Glut-1, glucocorticoid and mineralocorticoid receptors, proteins of the MAPK pathways and calcineurin were studied. Cortisol levels were 8.7 +/- 2.3 nM (SE) in 8 control and 1,028 +/- 189 nM in 9 treated fetuses (P < 0.001). Cortisol had no effect on myocyte binucleation. Left ventricular free wall (LVFW) uni- and binucleated myocytes were larger in cortisol-treated fetuses (P < 0.001, P < 0.05). Cortisol-treated fetuses had higher right ventricular free wall (RVFW) and LVFW angiotensinogen (Aogen) mRNA levels (treated: 2.30 +/- 0.37, n = 8 and 2.05 +/- 0.45, n = 7 vs. control: 0.94 +/- 0.12, n = 8 and 0.67 +/- 0.09, n = 7, P < 0.02). Levels of the glucose transporter Glut-1 mRNA were lower in the LVFW of treated fetuses (0.83 +/- 0.23 vs. 1.47 +/- 0.30 in control, P < 0.05, n = 7, 8). The higher the cortisol level, the greater the Aogen mRNA level (RVFW, r = 0.61, P < 0.01, n = 16; LVFW, r = 0.83, P < 0.0003, n = 14). There were no other changes in mRNA levels nor in levels of extracellular kinase, JNK, p38, their phosphorylated forms, and calcineurin. Thus high levels of cortisol such as occur after birth do not affect fetal cardiac myocyte binucleation or number but are associated with higher levels of ventricular Aogen mRNA, lower levels of Glut-1 mRNA, and hypertrophy of LVFW myocytes. These effects could impact on postnatal cardiac development.
Authors:
E R Lumbers; A C Boyce; G Joulianos; V Kumarasamy; E Barner; J L Segar; J H Burrell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2004-12-02
Journal Detail:
Title:  American journal of physiology. Regulatory, integrative and comparative physiology     Volume:  288     ISSN:  0363-6119     ISO Abbreviation:  Am. J. Physiol. Regul. Integr. Comp. Physiol.     Publication Date:  2005 Mar 
Date Detail:
Created Date:  2005-02-08     Completed Date:  2005-03-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  100901230     Medline TA:  Am J Physiol Regul Integr Comp Physiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  R567-74     Citation Subset:  IM    
Affiliation:
Dept. of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, NSW 2052, Australia. E.Lumbers@unsw.edu.au
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MeSH Terms
Descriptor/Qualifier:
Angiotensinogen / genetics
Animals
Cell Division / drug effects
Cell Nucleus / ultrastructure
Fetal Development
Fetal Heart / drug effects*,  metabolism*
Fetus
Gene Expression / drug effects
Glucose Transporter Type 1
Heart Ventricles
Hydrocortisone / blood,  pharmacology*
Hypertrophy
Monosaccharide Transport Proteins / genetics
Myocytes, Cardiac / drug effects*,  pathology,  ultrastructure
RNA, Messenger / metabolism
Renin-Angiotensin System / drug effects
Sheep
Chemical
Reg. No./Substance:
0/Glucose Transporter Type 1; 0/Monosaccharide Transport Proteins; 0/RNA, Messenger; 11002-13-4/Angiotensinogen; 50-23-7/Hydrocortisone

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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