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Increased production of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney microsomes of squirrel monkeys (Saimiri spp.).

ABSTRACT: In squirrel monkeys (Saimiri spp.), cortisol circulates at levels much higher than those seen in man and other Old World primates, but squirrel monkeys exhibit no physiologic signs of the mineralocorticoid effects of cortisol. These observations suggest that squirrel monkeys have mechanisms for protection of the mineralocorticoid receptor (MR) from these high levels of cortisol. We previously showed that the serum cortisol to cortisone ratio in these animals is low relative to that in human serum, suggesting that production of the MR protective enzyme, 11beta-hydroxysteroid dehydrogenase type 2 (11beta-HSD2), is increased in squirrel monkeys. Here, we directly evaluate whether increased production of 11beta-HSD2, which inactivates cortisol to cortisone, is a mechanism for protection of MR. In vitro assays showed that 11beta-HSD2 activity in squirrel monkey kidney microsomes was 3 to 7 times higher than that seen in kidney microsomes from pig or rabbit. 11beta-HSD2 protein detected by Western blot analysis was 4 to 9 times greater in squirrel monkey microsomes than in pig or rabbit microsomes. Comparison of the effect of expression of either human or squirrel monkey 11beta-HSD2 on MR transactivation activity showed similar inhibition of MR response to cortisol by both enzymes, indicating that the intrinsic activities of the human and squirrel monkey enzymes are similar. These findings suggest that one mechanism by which squirrel monkeys protect the MR from activation by high cortisol levels in the kidney is by upregulation of 11beta-HSD2 activity through increased production of the enzyme.

SUBMITTER: Sadosky PW

PROVIDER: S-EPMC2703166 | biostudies-literature | 2008 Apr

REPOSITORIES: biostudies-literature

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Increased production of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney microsomes of squirrel monkeys (Saimiri spp.).

Sadosky Patti W PW Scammell Jonathan G JG

Comparative medicine 20080401 2

In squirrel monkeys (Saimiri spp.), cortisol circulates at levels much higher than those seen in man and other Old World primates, but squirrel monkeys exhibit no physiologic signs of the mineralocorticoid effects of cortisol. These observations suggest that squirrel monkeys have mechanisms for protection of the mineralocorticoid receptor (MR) from these high levels of cortisol. We previously showed that the serum cortisol to cortisone ratio in these animals is low relative to that in human seru ...[more]

PMID: 18524177

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Project description:BackgroundEchocardiography is the most frequently used non -invasive diagnostic tool to evaluate cardiac anatomy and function in domestic species but increasingly also in non -domestic species, especially since cardiac disease is being recognized as an important cause of death in captive primates. The purpose of this cross -sectional study was to investigate the feasibility of transthoracic echocardiography in healthy squirrel monkeys as well as to provide species specific normal values for standard echocardiographic measurements. A secondary aim was to determine plasma and serum levels of the cardiac biomarkers, N -terminal pro -brain natriuretic peptide (NT -proBNP) and cardiac troponin T (cTnT). Furthermore, a commercial, non -invasive, smartphone -based ECG (AliveCor Vet TM) monitoring device was used to evaluate the heart rate and rhythm and to diagnose possible arrhythmias.ResultsIn this study, transthoracic echocardiography of 14 squirrel monkeys was performed in right and left lateral recumbency. Similar standard right parasternal and left apical images were obtained as in dogs and cats and normal values for routine two -dimensional, time motion mode and Doppler mode measurements were generated. Thirteen animals were considered healthy and one squirrel monkey was identified with significant aortic dilation and regurgitation and consequently values obtained from this animal were not used when species specific normal values were calculated. NT -ProBNP and cTnT concentrations were available for 7 of the 13 healthy monkeys with NT -proBNP concentrations below detection limit in all animals and a mean cTnT concentration of 0.049 ng/mL. Electrocardiography was performed in all squirrel monkeys. The mean heart rate was 172 bpm. Frequent supraventricular premature beats were diagnosed in the squirrel monkey suffering from significant aortic dilation and regurgitation.ConclusionThis study presents echocardiographic normal values and additional cardiovascular data in anaesthetised Saimiri monkeys, fundamental from both the perspective of zoo animal health care as well as scientific research, since the squirrel monkey is often used as an animal model for human disease.

Dataset Information

Increased production of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney microsomes of squirrel monkeys (Saimiri spp.).

Publications

Increased production of 11beta-hydroxysteroid dehydrogenase type 2 in the kidney microsomes of squirrel monkeys (Saimiri spp.).

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