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Science 28 October 1988:
Vol. 242. no. 4878, pp. 583 - 585
DOI: 10.1126/science.2845584

Articles

Science, Vol 242, Issue 4878, 583-585
Copyright © 1988 by American Association for the Advancement of Science


articles

Mineralocorticoid action: target tissue specificity is enzyme, not receptor, mediated

JW Funder, PT Pearce, R Smith, and AI Smith

Medical Research Centre, Prince Henry's Hospital, Melbourne, Australia.

Mineralocorticoid receptors, both when in tissue extracts and when recombinant-derived, have equal affinity for the physiological mineralocorticoid aldosterone and for the glucocorticoids cortisol and corticosterone, which circulate at much higher concentrations than aldosterone. Such receptors are found in physiological mineralocorticoid target tissues (kidney, parotid, and colon) and in nontarget tissues such as hippocampus and heart. In mineralocorticoid target tissues the receptors are selective for aldosterone in vivo because of the presence of the enzyme 11 beta-hydroxy-steroid dehydrogenase, which converts cortisol and corticosterone, but not aldosterone, to their 11-keto analogs. These analogs cannot bind to mineralocorticoid receptors.


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G. G. Lavery, V. Ronconi, N. Draper, E. H. Rabbitt, V. Lyons, K. E. Chapman, E. A. Walker, C. L. McTernan, G. Giacchetti, F. Mantero, et al. (2003)
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Transgenic Model of Aldosterone-Driven Cardiac Hypertrophy and Heart Failure.
W. Qin, A. E. Rudolph, B. R. Bond, R. Rocha, E. A.G. Blomme, J. J. Goellner, J. W. Funder, and E. G. McMahon (2003)
Circ. Res. 93, 69-76
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Inhibition of 11{beta}-hydroxysteroid dehydrogenase type 1 lowers intraocular pressure in patients with ocular hypertension.
S. Rauz, C.M.G. Cheung, P.J. Wood, M. Coca-Prados, E.A. Walker, P.I. Murray, and P.M. Stewart (2003)
QJM 96, 481-490
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3-Methylindole Induces Transient Olfactory Mucosal Injuryin Ponies.
M. A. Miller, S. J. Kottler, J. A. Ramos-Vara, P. J. Johnson, V. K. Ganjam, and T. J. Evans (2003)
Vet. Pathol. 40, 363-370
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Localization of 11{beta}-Hydroxysteroid Dehydrogenase Types 1 and 2 in the Male Reproductive Tract.
B. J. Waddell, S. Hisheh, Z. S. Krozowski, and P. J. Burton (2003)
Endocrinology 144, 3101-3106
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Hypertension and the Cortisol-Cortisone Shuttle.
M. Quinkler and P. M. Stewart (2003)
J. Clin. Endocrinol. Metab. 88, 2384-2392
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Two Homozygous Mutations in the 11{beta}-Hydroxysteroid Dehydrogenase Type 2 Gene in a Case of Apparent Mineralocorticoid Excess.
C. A. Carvajal, A. A. Gonzalez, D. G. Romero, A. Gonzalez, L. M. Mosso, E. T. Lagos, M. d. P. Hevia, M. P. Rosati, T. O. Perez-Acle, C. E. Gomez-Sanchez, et al. (2003)
J. Clin. Endocrinol. Metab. 88, 2501-2507
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The Human Kidney Is a Progesterone-Metabolizing and Androgen-Producing Organ.
M. Quinkler, C. Bumke-Vogt, B. Meyer, V. Bahr, W. Oelkers, and S. Diederich (2003)
J. Clin. Endocrinol. Metab. 88, 2803-2809
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11{beta}-Hydroxysteroid Dehydrogenase Complementary Deoxyribonucleic Acid in Rainbow Trout: Cloning, Sites of Expression, and Seasonal Changes in Gonads.
M. Kusakabe, I. Nakamura, and G. Young (2003)
Endocrinology 144, 2534-2545
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Leptin Activation of Corticosterone Production in Hepatocytes May Contribute to the Reversal of Obesity and Hyperglycemia in Leptin-Deficient ob/ob Mice.
Y. Liu, Y. Nakagawa, Y. Wang, R. Li, X. Li, T. Ohzeki, and T. C. Friedman (2003)
Diabetes 52, 1409-1416
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