Journal
MOLECULAR AND CELLULAR ENDOCRINOLOGY
Volume 265, Issue -, Pages 143-149Publisher
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2006.12.012
Keywords
CRH; CRH-R1; POMC; cutaneous steroidogenesis; cutaneous P450scc; stress response
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Funding
- NIAMS NIH HHS [AR047079, AR052190, R01 AR052190, R01 AR047079] Funding Source: Medline
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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.
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