HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/3/R567    most recent 00556.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (17) Citing Articles via Google Scholar Google Scholar Articles by Lumbers, E. R. Articles by Burrell, J. H. Search for Related Content PubMed PubMed Citation Articles by Lumbers, E. R. Articles by Burrell, J. H.

CALL FOR PAPERS
Fetal Physiological Programming

Effects of cortisol on cardiac myocytes and on expression of cardiac genes in fetal sheep

¹Department of Physiology and Pharmacology, School of Medical Sciences, University of New South Wales, Sydney, Australia; and ²Department of Pediatrics, University of Iowa, Iowa City, Iowa

Submitted 16 August 2004 ; accepted in final form 22 November 2004

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.

angiotensinogen; Glut-1 mRNA

This article has been cited by other articles:

				A. J. Forhead, S. Cutts, P. A. Matthews, and A. L. Fowden Role of thyroid hormones in the developmental control of tissue glycogen in fetal sheep near term Exp Physiol, October 1, 2009; 94(10): 1079 - 1087. [Abstract] [Full Text] [PDF]

				A. L. Fowden and A. J. Forhead Hormones as epigenetic signals in developmental programming Exp Physiol, June 1, 2009; 94(6): 607 - 625. [Abstract] [Full Text] [PDF]

				E. R. Lumbers, M. y. Kim, J. H. Burrell, V. Kumarasamy, A. C. Boyce, K. J. Gibson, K. L. Gatford, and J. A. Owens Effects of intrafetal IGF-I on growth of cardiac myocytes in late-gestation fetal sheep Am J Physiol Endocrinol Metab, March 1, 2009; 296(3): E513 - E519. [Abstract] [Full Text] [PDF]

				J. L. Morrison, K. J. Botting, J. L. Dyer, S. J. Williams, K. L. Thornburg, and I. C. McMillen Restriction of placental function alters heart development in the sheep fetus Am J Physiol Regulatory Integrative Comp Physiol, July 1, 2007; 293(1): R306 - R313. [Abstract] [Full Text] [PDF]

				S. Louey, S. S. Jonker, G. D. Giraud, and K. L. Thornburg Placental insufficiency decreases cell cycle activity and terminal maturation in fetal sheep cardiomyocytes J. Physiol., April 15, 2007; 580(2): 639 - 648. [Abstract] [Full Text] [PDF]

				S. S. Jonker, L. Zhang, S. Louey, G. D. Giraud, K. L. Thornburg, and J. J. Faber Myocyte enlargement, differentiation, and proliferation kinetics in the fetal sheep heart J Appl Physiol, March 1, 2007; 102(3): 1130 - 1142. [Abstract] [Full Text] [PDF]

				S. S. Jonker, J. J. Faber, D. F. Anderson, K. L. Thornburg, S. Louey, and G. D. Giraud Sequential growth of fetal sheep cardiac myocytes in response to simultaneous arterial and venous hypertension Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2007; 292(2): R913 - R919. [Abstract] [Full Text] [PDF]

				S. A. Reini, C. E. Wood, E. Jensen, and M. Keller-Wood Increased maternal cortisol in late-gestation ewes decreases fetal cardiac expression of 11beta-HSD2 mRNA and the ratio of AT1 to AT2 receptor mRNA Am J Physiol Regulatory Integrative Comp Physiol, December 1, 2006; 291(6): R1708 - R1716. [Abstract] [Full Text] [PDF]

				A. C. Boyce, K. J. Gibson, E. M. Wintour, I. Koukoulas, and E. R. Lumbers Effects of 7-day amino acid infusion on renal growth, function, and renin-angiotensin system in fetal sheep Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2005; 289(4): R1099 - R1106. [Abstract] [Full Text] [PDF]