Vitamin D receptor and enzyme expression in dorsal root ganglia of adult female rats: modulation by ovarian hormones.
Vitamin D insufficiency impacts sensory processes including pain and proprioception, but little is known regarding vitamin D signaling in adult sensory neurons. We analyzed female rat dorsal root ganglia (DRG) for vitamin receptor (VDR) and the vitamin D metabolizing enzymes CYP27B1 and CYP24. Western blots and immunofluorescence revealed the presence of these proteins in sensory neurons. Nuclear VDR immunoreactivity was present within nearly all neurons, while cytoplasmic VDR was found preferentially in unmyelinated calcitonin gene-related peptide (CGRP)-positive neurons, colocalizing with CYP27B1 and CYP24. These data suggest that 1,25(OH)(2)D3 may affect sensory neurons through nuclear or extranuclear signaling pathways. In addition, local vitamin D metabolite concentrations in unmyelinated sensory neurons may be controlled through expression of CYP27B1 and CYP24. Because vitamin D deficiency appears to exacerbate some peri-menopausal pain syndromes, we assessed the effect of ovariectomy on vitamin D-related proteins. Two weeks following ovariectomy, total VDR expression in DRG dropped significantly, owing to a slight decrease in the percentage of total neurons expressing nuclear VDR and a large drop in unmyelinated CGRP-positive neurons expressing cytoplasmic VDR. Total CYP27B1 expression dropped significantly, predominantly due to decreased expression within unmyelinated CGRP-positive neurons. CYP24 expression remained unchanged. Therefore, unmyelinated CGRP-positive neurons appear to have a distinct vitamin D phenotype with hormonally-regulated ligand and receptor levels. These findings imply that vitamin D signaling may play a specialized role in a neural cell population that is primarily nociceptive.
Department of Molecular and Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, USA.
Sarah E
SE
Tague
Peter G
PG
Smith
D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase / Q000378:metabolism*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002117:Calcitriol / Q000172:deficiency / Q000378:metabolism; D002467:Cell Nucleus / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism*; D007150:Immunohistochemistry; D036421:Nerve Fibers, Unmyelinated / Q000378:metabolism; D009619:Nociceptors / Q000378:metabolism*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013250:Steroid Hydroxylases / Q000378:metabolism*; D065668:Vitamin D3 24-Hydroxylase
D004967:Estrogens; D018167:Receptors, Calcitriol; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D015090:25-Hydroxyvitamin D3 1-alpha-Hydroxylase; D002117:Calcitriol; D015740:Calcitonin Gene-Related Peptide