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Steroidogenesis in the skin: implications for local immune functions
Andrzej Slominski1, Blazej Zbytek, Georgios Nikolakis
1Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Center for Cancer Research, University of Tennessee Health Science Center, Memphis, TN 38163, USA; Department of Medicine, University of Tennessee Health Science Center, Memphis, TN 38163, USA.
The Journal of Steroid Biochemistry and Molecular Biology
|February 26, 2013
Summary
The skin functions as an independent steroidogenic organ, producing its own glucocorticoids, androgens, and estrogens. This local steroid production impacts skin health and immune function, offering new therapeutic avenues for skin disorders.
Area of Science:
- Dermatology
- Endocrinology
- Immunology
Background:
- The skin possesses immune and steroidogenic functions crucial for homeostasis and protection.
- Skin cells can synthesize glucocorticoids, androgens, and estrogens from precursors or cholesterol.
- Local steroid production is regulated by hormones like CRH and ACTH, and cytokines, and influenced by UV radiation.
Purpose of the Study:
- To explore the skin's capacity for local steroid production (steroidogenesis).
- To understand the regulation and functional impact of cutaneous steroids on skin immunity and homeostasis.
- To investigate the therapeutic potential of modulating skin steroidogenesis.
Main Methods:
- Review of existing literature on skin steroidogenesis.
- Analysis of biochemical pathways for steroid synthesis in skin cells.
- Examination of the regulatory mechanisms of cutaneous steroid production.
Main Results:
- Skin cells possess the complete machinery for synthesizing active steroids like cortisol, testosterone, and estradiol.
- Local steroid production varies by skin compartment and cell type.
- Cutaneous steroids influence epidermal and adnexal functions, as well as local immune responses.
Conclusions:
- The skin acts as an independent steroidogenic organ.
- Dysfunctional skin steroidogenesis is linked to inflammatory and autoimmune skin diseases.
- Modulating skin steroidogenesis presents a promising therapeutic strategy for various skin conditions.
Keywords:
11-hydroxysteroiddehydrogenase type 111-hydroxysteroiddehydrogenase type 211β-hydroxylase type 111β-hydroxylase type 217β-HSD17β-hydroxysteroid dehydrogenase21-hydroxylase3α-HSD3α-hydroxysteroid dehydrogenase3β-HSD3β-hydroxysteroid dehydrogenase5α-reductase5αRACTHAndrogenCDCRHCYP11A1CYP11A1 or P450sccCYP11B1CYP11B2CYP17A1 or P450c17CYP21DAX-1DHEADHTDOCDPCsE1E2ECMEREERREstrogenGM-CSFGRGlucocorticoidsHFHPAHSHSD11B1 or 11-HSD 1HSD11B2 or 11-HSD 2INFIRSKSLEMHCMRNFkBNHEKsORSKsPOMCSF-1SPSScSkin endocrine systemSkin immune systemStARTT helperTGFβThUVRadrenocorticotropic hormonecAMP-dependent protein kinase AcAMP/PKAcluster of differentiationcorticotrophin releasing hormonecytochrome P450 17α-hydroxylase/17,20-lyasecytochrome P450 side-chain cleavage enzymedehydroepiandrosteronedeoxycorticosteronedermal papilla cellsdihydrotestosteronedosage-sensitive sex-reversal-adrenal hypoplasia congenital critical region on the x-chromosome, gene 1estradiolestrogen response elementestrogen-related receptorestroneextracellular matrixglucocorticoid receptorgranulocyte-macrophage colony-stimulating factorhair folliclehidradenitis suppurativa/acne inversahypothalamus–pituitary–adrenal glandinner root sheath keratinocytesinterferonlupus erythematosusmajor histocompatibility complexmineralocorticoid receptornormal human epidermal keratinocytesnuclear factor kappa-light-chain-enhancer of activated B cellsouter root sheath keratinocytesproopiomelanocortinsteroidogenic acute regulatory proteinsteroidogenic factor 1substance Psystemic sclerosistestosteronetransforming growth factor βultraviolet radiationRelated Concept Videos
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