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Corticotropin-releasing factor receptor 2 (CRF-R-2) (CRF-R2) (CRFR-2) (Corticotropin-releasing hormone receptor 2) (CRH-R-2) (CRH-R2) [CRF2R] [CRH2R]


Aging-related changes in cutaneous corticotropin-releasing hormone system reflect a defective neuroendocrine-stress response in aging.

Skin, being a mirror of the body, is a major target for aging research. Aging is a complex process that involves the decline of function or dysfunction of many systems. The corticotropin-releasing hormone (CRH) system is involved in skin inflammation. In addition, CRH has a suggested role in age-associated conditions and in animal aging models. However, a consistent logic interaction between the different CRH system components and the aging process has, to our knowledge, never been examined before. The expression of CRH, CRH-binding protein ([[CRHBP]]), CRH receptor 1 (CRHR1), and CRH receptor 2 ([[CRHR2]]) in healthy skin samples of 42 patients of different ages (18-92 years) was evaluated by immunohistochemistry, and the age-related changes were assessed. Compared with young skin, the aged skin displayed an upregulation of CRH in sebaceous glands and CRHR1 in hair follicles and the epidermis. Moreover, age-associated downregulation of [[CRHBP]] in the sebaceous and sweat glands was detected, whereas the [[CRHR2]] showed no age-related changes. Our findings suggest that the age-associated changes in the expression of CRH system components reflect an exaggerated stress response reaction, putting the aged skin continuously in a stress-like situation.

MeSH Terms

  • Adult
  • Aged
  • Aging
  • Carrier Proteins
  • Corticotropin-Releasing Hormone
  • Female
  • Humans
  • Male
  • Middle Aged
  • Receptors, Corticotropin-Releasing Hormone
  • Sebaceous Glands
  • Skin
  • Stress, Physiological
  • Young Adult

Corticotropin-releasing hormone receptor-1 in cerebral microvessels changes during development and influences urocortin transport across the blood-brain barrier.

In this study we tested the hypothesis that receptor-mediated transport of urocortin across the blood-brain barrier (BBB) undergoes developmental changes. Urocortin is a peptide produced by both selective brain regions and peripheral organs, and it is involved in feeding, memory, mood, cardiovascular functions, and immune regulation. In BBB studies with multiple-time regression analysis, we found that neonatal mice had a significant influx of (125)I-urocortin. By contrast, adult mice did not transport urocortin across the BBB. Quantitative RT-PCR showed that corticotropin-releasing hormone receptor (CRHR)-1 was developmentally regulated in enriched cerebral microvessels as well as hypothalamus, being significantly higher in neonatal than adult mice. This change was less dramatic in agouti viable yellow mice, a strain that develops adult-onset obesity. The level of expression of CRHR1 mRNA was 33-fold higher in the microvessels than in hypothalamic homogenates. The mRNA for [[CRHR2]] was less abundant in both regions and less prone to changes with development or the agouti viable yellow mutation. Supported by previous findings of receptor-mediated endocytosis of urocortin, these results suggest that permeation of urocortin across the BBB is dependent on the level of CRHR1 expression in cerebral microvessels. These novel findings of differential regulation of CRH receptor subtypes help elucidate developmental processes in the brain, particularly for the urocortin system.

MeSH Terms

  • Aging
  • Animals
  • Animals, Newborn
  • Blood-Brain Barrier
  • Female
  • Hypothalamus
  • Iodine Radioisotopes
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Microvessels
  • Protein Isoforms
  • Receptors, Corticotropin-Releasing Hormone
  • Urocortins