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Corticosteroids, receptors, and the organ‐specific functions of 11 β ‐hydroxysteroid dehydrogenase
Author(s) -
Monder Carl
Publication year - 1991
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.5.15.1743437
Subject(s) - mineralocorticoid , mineralocorticoid receptor , endocrinology , medicine , aldosterone , receptor , testosterone (patch) , glucocorticoid receptor , glucocorticoid , enzyme , biology , dehydrogenase , beta (programming language) , biochemistry , computer science , programming language
Reversible oxidation of the biologically active corticosteroids to the inactive 11‐dehydrocorticosteroids is catalyzed by 11 β ‐hydroxysteroid dehydrogenase (11 β HSD). The properties of the enzyme based on clinical observations of individuals with defective 11 β HSD expression, and laboratory studies of the properties and behavior of the enzyme, are consistent with separate 11 β ‐dehydrogenase and 11‐oxoreductase species. However, recombinant enzyme expressed in mammalian cells retain both activities, leading to the conclusion that 11 β HSD is a unique, reversible enzyme. 11 β HSD is present in most tissues, but its specific functions in most tissues are unknown. How the enzyme may mediate corticosteroid‐receptor interaction is illustrated by studies using kidney, testis, and brain. In kidney, 11 β HSD prevents glucocorticoids from competing inappropriately with aldosterone for mineralocorticoid receptor (MR). Lack of enzyme in humans due to natural causes or inhibition by pharmacological agents results in maximum activation of MR by glucocorticoids, leading to the clinical symptoms of apparent mineralocorticoid excess. Leydig cells of the testes synthesize testosterone, a process that is suppressed by events initiated by the binding of corticosteroid to glucocorticoid receptors (GR). Depletion of active steroid mediated by 11 β SHSD may initiate testosterone production at puberty and affect testosterone production during adult life, as for example during periods of stress. The heterogeneous distribution of MR and GR in the brain reflects the specific regional effects of glucocorticoids and mineralocorticoids on neural function. Colocalization of 11 β HSD and corticosteroid receptors in brain may be important in controlling the specificity of corticosteroid interaction with GR and MR. The patterns of 11 β HSD‐steroid‐receptor interaction illustrated with these three tissues may provide models applicable to other tissues in which corticosteroid receptors and 11 β HSD coexist.— Monder, C. Corticosteroids, receptors, and the organ‐specific functions of 11 β ‐hydroxysteroid dehydrogenase. FASEB J. 5: 3047‐3054; 1991.