CRH stimulation of corticosteroids production in melanocytes is mediated by ACTH.
The response to systemic stress is organized along the hypothalamic-pituitary-adrenal axis (HPA), whereas the response to a peripheral stress (solar radiation) is mediated by epidermal melanocytes (cells of neural crest origin) responsible for the pigmentary reaction. Melanocytes express proopiomelanocortin (POMC), corticotropin-releasing hormone (CRH), and CRH receptor-1 (CRH-R1) and can produce corticosterone. In the present study, incubation of normal epidermal melanocytes with CRH was found to trigger a functional cascade structured hierarchically and arranged along the same algorithm as in the HPA axis: CRH activation of CRH-R1 stimulated cAMP accumulation and increased POMC gene expression and production of ACTH. CRH and ACTH also enhanced production of cortisol and corticosterone, and cortisol production was also stimulated by progesterone. The chemical identity of the cortisol was confirmed by liquid chromatography-mass spectrometry (LC/MS2) with [corrected] mass spectrometry-mass spectrometry analyses. POMC gene silencing abolished the stimulatory effect of CRH on corticosteroid synthesis, indicating that this is indirect and mediated via production of ACTH. Thus the melanocyte response to CRH is highly organized along the same functional hierarchy as the HPA axis. This pattern demonstrates the fractal nature of the response to stress with similar activation sequence at the single-cell and whole body levels.
Slominski
Andrzej
A
Department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, 930 Madison Ave. Room 519, Memphis, TN 38103, USA. aslominski@utmem.edu
Zbytek
Blazej
B
Szczesniewski
Andrzej
A
Semak
Igor
I
Kaminski
Jan
J
Sweatman
Trevor
T
Wortsman
Jacobo
J
D000305:Adrenal Cortex Hormones / Q000096:biosynthesis*; D000324:Adrenocorticotropic Hormone / Q000096:biosynthesis*; D003346:Corticotropin-Releasing Hormone / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism; D008401:Gas Chromatography-Mass Spectrometry; D020868:Gene Silencing / Q000502:physiology; D006801:Humans; D006854:Hydrocortisone / Q000096:biosynthesis; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects / Q000378:metabolism; D008544:Melanocytes / Q000187:drug effects* / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000187:drug effects / Q000378:metabolism; D011333:Pro-Opiomelanocortin / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D018019:Receptors, Corticotropin-Releasing Hormone / Q000096:biosynthesis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012867:Skin / Q000166:cytology
D000305:Adrenal Cortex Hormones; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; D011333:Pro-Opiomelanocortin; D000324:Adrenocorticotropic Hormone; D003346:Corticotropin-Releasing Hormone; D000242:Cyclic AMP; D006854:Hydrocortisone