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Journal of Endocrinology (2006) 191, 171-177    DOI: 10.1677/joe.1.06815
© 2006 Society for Endocrinology

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Regulation of adrenomedullin release from human endothelial cells by sex steroids and angiotensin-II

Lachlan J Pearson, Christopher Rait, M Gary Nicholls1, Timothy G Yandle1 and John J Evans

Department of Obstetrics and Gynaecology and
1 Department of Medicine, Christchurch School of Medicine and Health Sciences, University of Otago, Christchurch, New Zealand

(Requests for offprints should be addressed to J J Evans; Email: john.evans{at}chmeds.ac.nz)

It is well documented that there are gender differences in the incidence and patterns of cardiovascular diseases but the reasons are unclear. Sex steroids may modulate the behaviour of vascular endothelial cells, which in turn act by paracrine processes to alter adjacent vascular smooth muscle activity. We hypothesised that the sex steroids alter the percentage of vascular endothelial cells that secrete the vasodilator peptide, adrenomedullin and modify the adrenomedullin-stimulating action of angiotensin-II. The percentage of adrenomedullin-secreting human aortic endothelial cells was determined using the cell immunoblot method. Cells were incubated with selected concentrations of angiotensin-II, oestradiol and testosterone alone and sex steroids in combination with angiotensin-II. Adrenomedullin mRNA expression in endothelial cells was quantified by real-time PCR. It was observed that at 4 h, angiotensin-II increased the percentage of adrenomedullin-secreting cells in a concentration-dependent manner. Testosterone at physiological concentrations was observed to increase the number of adrenomedullin-secreting cells whilst oestradiol had no effect. Addition of testosterone to angiotensin-II resulted in less than additive increases in the number of cells secreting adrenomedullin. Oestradiol reduced the angiotensin-II-induced increase in adrenomedullin-secreting cells. Adrenomedullin mRNA expression was significantly increased by testosterone and there was also a trend for an increase in adrenomedullin mRNA expression, which occurred when cells were incubated with angiotensin-II. Our results point to a complex interplay between the sex steroids and angiotensin-II in regulating adrenomedullin production by human endothelial cells, which may contribute to gender-related differences in vascular disease in humans.




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K. Caron, J. Hagaman, T. Nishikimi, H.-S. Kim, and O. Smithies
Adrenomedullin gene expression differences in mice do not affect blood pressure but modulate hypertension-induced pathology in males
PNAS, February 27, 2007; 104(9): 3420 - 3425.
[Abstract] [Full Text] [PDF]




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