Human skin as target for aldosterone: coexpression of mineralocorticoid receptors and 11 beta-hydroxysteroid dehydrogenase.
The expression of mineralocorticoid receptors (MR) and 11 beta-hydroxysteroid dehydrogenase (11HSD) activity has been investigated in the epidermis and appendages of the human skin. Aldosterone binds to MR and regulates sodium transport in tight epithelia. Mineralocorticoid selectivity is achieved through coexpression of MR and 11HSD, which prevents permanent MR occupancy by glucocorticoids. Some forms of hypertension may involve abnormalities of MR and/or 11HSD. However, their direct assessment in humans remains difficult in the kidney or colon. This led us to explore this system in human skin easily accessible to biopsy. In situ hybridization with specific MR complementary ribonucleic acid probes and immunohistochemistry using three different anti-MR antibodies showed that MR was expressed at both the messenger ribonucleic acid and protein levels in the keratinocytes of the epidermis, in the sweat and sebaceous glands, and in the hair follicles. A significant 11HSD activity was found in isolated sweat gland ducts (5 fmol/3-mm length.10-min incubation with 10 nmol/L corticosterone as substrate) and was very low in the epidermis. In both structures, reductase activity was 10 times lower than that of dehydrogenase. Studies on the cofactor specificity of the enzyme showed a nicotinamide-adenine-dinucleotide preference in sweat glands, contrasting with a nicotinamide-adenine-dinucleotide phosphate dependence in epidermis. Human skin appears as a new target for aldosterone because it coexpresses MR and 11HSD. Our findings present the possibility to explore the functionality of the MR system in human tissue and its implications in various physiopathological situations.
INSERM U-246, Faculté de Médecine Xavier Bichat, Paris, France.
S
S
Kenouch
M
M
Lombes
F
F
Delahaye
E
E
Eugene
J P
JP
Bonvalet
N
N
Farman
D042842:11-beta-Hydroxysteroid Dehydrogenases; D000450:Aldosterone / Q000494:pharmacology*; D005786:Gene Expression Regulation; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D006913:Hydroxysteroid Dehydrogenases / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D018161:Receptors, Mineralocorticoid / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D012867:Skin / Q000737:chemistry / Q000187:drug effects* / Q000648:ultrastructure; D013545:Sweat Glands / Q000201:enzymology
D012333:RNA, Messenger; D018161:Receptors, Mineralocorticoid; D000450:Aldosterone; D006913:Hydroxysteroid Dehydrogenases; D042842:11-beta-Hydroxysteroid Dehydrogenases