Differential expression of HPA axis homolog in the skin

Differential expression of HPA axis homolog in the skin
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DOI:
10.1016/j.mce.2006.12.012
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发表时间:
2007-02-01
影响因子:
4.1
通讯作者:
Paus, Ralf
Paus, Ralf
中科院分区:
医学2区
文献类型:
--
作者:
Slominski, Andrzej;Wortsman, Jacobo;Paus, Ralf

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Human skin expresses elements of the hypothalamo-pituitary-adrenal (HPA) axis including pro-opiomelanocortin (POMC), corticotropin releasing hormone (CRH), the CRH receptor-1 (CRH-R1), key enzymes of corticosteroid synthesis and synthesizes glucocorticoids. Expression of these elements is organized in functional, cell type-specific regulatory loops, which imitate the signaling hierarchy of the HPA axis. In melanocytes and fibroblasts CRH-induced CRH-R1 stimulation upregulates POMC expression and production of ACTH through activation of cAMP dependent pathway(s). Melanocytes respond with enhanced production of cortisol and corticosterone, which is dependent on POMC activity. Fibroblasts respond to CRH and ACTH with enhanced production of corticosterone, but not cortisol, which is produced constitutively. Organ-cultured human scalp hair follicles also show a fully functional HPA axis equivalent, including cortisol synthesis and secretion and negative feedback regulation by cortisol on CRH expression. Thus, differential, CRH-driven responses of defined cutaneous cell populations reproduce key features of the central HPA axis at the tissue/single cell levels. (c) 2007 Elsevier Ireland Ltd. All rights reserved.