Immunolocalization of enzymes, binding proteins, and receptors sufficient for retinoic acid synthesis and signaling during the hair cycle

J Invest Dermatol. 2007 Jul;127(7):1593-604. doi: 10.1038/sj.jid.5700753. Epub 2007 Mar 15.

Abstract

Retinoic acid (RA) is essential for maintenance of most epithelial tissues. One RA biosynthesis pathway consists of cellular retinol-binding protein (Crbp), retinol dehydrogenase (Dhrs9/eRoldh), retinal dehydrogenase 1-3 (Aldh1a1-3), and cellular RA-binding protein 2 (Crabp2). Previously, we localized Aldh1a2 and Aldh1a3 to both epithelial and mesenchymal cells within the hair follicle throughout the hair cycle. This study expands that observation by examining the complete pathway of RA biosynthesis and signaling via RA receptors alpha, beta, and gamma by immunohistochemistry in C57BL/6J mice wax-stripped to initiate and synchronize the cycle. This pathway of RA biosynthesis and signaling localized to the majority of layers of the hair follicle, sebaceous gland, and interfollicular epidermis in a hair cycle-dependent manner, suggesting that RA biosynthesis within the hair follicle is regulated in both a spatial and temporal manner. This localization pattern also revealed insights into epithelial-mesenchymal interactions and differentiation state differences within the RA biosynthesis and signaling pathway, as well as novel observations on nuclear versus cytoplasmic localization of Crabp2 and RA receptors. This complex pattern of RA biosynthesis and signaling identified by immunolocalization suggests that endogenous RA regulates specific aspects of hair follicle growth, differentiation, and cycling.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcohol Oxidoreductases / genetics
  • Alcohol Oxidoreductases / physiology
  • Animals
  • Cell Communication / physiology
  • Cell Cycle / physiology*
  • Cell Differentiation / physiology
  • Epidermal Cells
  • Epidermis / physiology
  • Female
  • Hair / cytology
  • Hair / physiology*
  • Hair Follicle / cytology
  • Hair Follicle / physiology
  • Immunohistochemistry
  • Mesoderm / cytology
  • Mesoderm / physiology
  • Mice
  • Mice, Inbred C57BL
  • Rabbits
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / physiology*
  • Retinoic Acid Receptor alpha
  • Retinoic Acid Receptor gamma
  • Retinol-Binding Proteins / genetics
  • Retinol-Binding Proteins / physiology
  • Retinol-Binding Proteins, Cellular
  • Signal Transduction / physiology
  • Tretinoin / metabolism*

Substances

  • Rara protein, mouse
  • Receptors, Retinoic Acid
  • Retinoic Acid Receptor alpha
  • Retinol-Binding Proteins
  • Retinol-Binding Proteins, Cellular
  • retinoic acid binding protein II, cellular
  • retinoic acid receptor beta
  • Tretinoin
  • Alcohol Oxidoreductases
  • retinol dehydrogenase