Species diversity of 11β-hydroxysteroid dehydrogenase in the cardiovascular system

Simon Slight, Venkataseshu K. Ganjam, Karl Weber

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Mineralocorticoid (MC) receptors are found in classic (e.g., kidney) and nonclassic (e.g., heart and aorta) tissues. MC receptor specificity at either site is conferred by the enzyme 11β-hydroxysteroid dehydrogenase (11β-HSD), which metabolizes glucocorticoids to inactive 11-ketosteroids. Because the heart and vasculature may be target tissues for aldosterone, this study was undertaken. Its objectives were to measure 11β-HSD at these sites and to compare levels of activity in the atria and ventricles of different species. Toward this end we first determined levels of plasma corticosterone (B) and cortisol (F) (by using radioimmunoassay), in a variety of species, for subsequent correlation with cardiac 11β-HSD activity. 11β-Dehydrogenation of glucocorticoids was then assayed in ventricles and atria as well as aorta. Tissue homogenates containing 1 to 5 mg protein were incubated for 1 hour in the presence of 1 μCi 5 × 10-9 mol/L tritiated B or tritiated F and 5 × 10-4 mol/L oxidized nicotinamide adenine dinucleotide phosphate. Steroid separation and quantitation were achieved by using reverse-phase high-performance liquid chromatography coupled to an online radioisotope detector. For species in which B circulates at relatively high concentrations (rat, rabbit, pig), high levels of dehydrogenation of B to 11-dehydrocorticosterone (A) were observed in both atria and ventricles. Overall, cardiac B to A conversion levels corresponded to between 0.3 and 0.4 pmol A formed/mg protein/hr. 11β-HSD activity was also detected in the aorta. In the rat heart, 11-oxoreduction of A to B was equivalent to 11-dehydrogenation of B to A, strongly suggesting that 11β-HSD is a bidirectional enzyme possessing both 11β-dehydrogenase and 11-oxoreductase activities. 11β-Dehydrogenation of B was approximately 10 times lower in species in which F is the dominant glucocorticoid (human, ox, horse, dog). No conversion of F to cortisone (E) was observed in cardiac or aortic homogenates of any species investigated. Thus, 11β-HSD activity is present in cardiovascular tissues and appears to be significantly higher in species in which B rather than F predominates in plasma. These findings show that diversity exists in the activity of this key guardian enzyme in the cardiovascular system of different species.

Original languageEnglish (US)
Pages (from-to)821-826
Number of pages6
JournalThe Journal of Laboratory and Clinical Medicine
Volume124
Issue number6
StatePublished - Jan 1 1994
Externally publishedYes

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11-beta-Hydroxysteroid Dehydrogenases
Cardiovascular system
Biodiversity
Cardiovascular System
Dehydrogenation
Tissue
Glucocorticoids
Aorta
Mineralocorticoid Receptors
Rats
Enzymes
Ketosteroids
Plasmas
Cortisone
High performance liquid chromatography
Reverse-Phase Chromatography
Corticosterone
Aldosterone
NADP
Radioisotopes

All Science Journal Classification (ASJC) codes

  • Pathology and Forensic Medicine

Cite this

Species diversity of 11β-hydroxysteroid dehydrogenase in the cardiovascular system. / Slight, Simon; Ganjam, Venkataseshu K.; Weber, Karl.

In: The Journal of Laboratory and Clinical Medicine, Vol. 124, No. 6, 01.01.1994, p. 821-826.

Research output: Contribution to journalArticle

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