Skobowiat Cezary, Slominski Andrzej T
Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, USA.
Department of Pathology and Laboratory Medicine, Center for Cancer Research, University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, USA; Division of Rheumatology, Department of Medicine, University of Tennessee Health Science Center (UTHSC), Memphis, Tennessee, USA.
J Invest Dermatol. 2015 Jun;135(6):1638-1648. doi: 10.1038/jid.2014.450. Epub 2014 Oct 15.
To test the hypothesis that UVB can activate the hypothalamic-pituitary-adrenal (HPA) axis, the shaved back skin of C57BL/6 mice was exposed to 400 mJ cm(-2) of UVB or was sham irradiated. After 12 and 24 hours of exposure, plasma, skin, brain, and adrenals were collected and processed to measure corticotropin-releasing hormone (CRH), urocortin (Ucn), β-endorphin (β-END), ACTH, and corticosterone (CORT) or the brain was fixed for immunohistochemical detection of CRH. UVB stimulated plasma levels of CRH, Ucn, β-END, ACTH, and CORT and increased skin expression of Ucn, β-END, and CORT at the gene and protein/peptide levels. UVB stimulated CRH gene and protein expression in the brain that was localized to the paraventricular nucleus of the hypothalamus. In adrenal glands, it increased mRNAs of melanocortin receptor type 2, steroidogenic acute regulatory protein (StAR), and gene coding of steroid 11β-hydroxylase (CYP11B1). Hypophysectomy abolished UVB stimulation of plasma, but not of skin CORT levels, and had no effect on UVB stimulation of CRH and Ucn levels in the plasma, demonstrating the requirement of an intact pituitary for the systemic effect. In conclusion, we identify mechanisms regulating body homeostasis by UVB through activation of the HPA axis that originate in the skin and require the pituitary for systemic effects.
为了验证紫外线B（UVB）可激活下丘脑-垂体-肾上腺（HPA）轴这一假说，将C57BL/6小鼠背部剃毛后的皮肤暴露于400 mJ cm(-2)的UVB下或进行假照射。暴露12小时和24小时后，收集血浆、皮肤、脑和肾上腺并进行处理，以检测促肾上腺皮质激素释放激素（CRH）、尿皮质素（Ucn）、β-内啡肽（β-END）、促肾上腺皮质激素（ACTH）和皮质酮（CORT），或者将脑固定用于CRH的免疫组织化学检测。UVB刺激了CRH、Ucn、β-END、ACTH和CORT的血浆水平，并在基因和蛋白质/肽水平上增加了皮肤中Ucn、β-END和CORT的表达。UVB刺激了脑中CRH的基因和蛋白质表达，其定位于下丘脑室旁核。在肾上腺中，它增加了2型黑皮质素受体、类固醇生成急性调节蛋白（StAR）和类固醇11β-羟化酶（CYP11B1）编码基因的mRNA水平。垂体切除消除了UVB对血浆CORT水平的刺激，但未消除对皮肤CORT水平的刺激，并且对UVB刺激血浆中CRH和Ucn水平没有影响，这表明全身效应需要完整的垂体。总之，我们确定了UVB通过激活起源于皮肤且全身效应需要垂体的HPA轴来调节身体内环境稳定的机制。
