| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 5, 2004
Accepted on December 2, 2004
Endocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston Massachusetts. Kennedy Krieger Institute and Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, Maryland. Department of Pharmacology, Case Western Reserve University, Cleveland, Ohio
* To whom correspondence should be addressed. E-mail: demay{at}helix.mgh.harvard.edu.
Alopecia is a feature of vitamin D receptor (VDR) mutations in humans and in VDR null mice. This alopecia results from an inability to initiate the anagen phase of the hair cycle after follicle morphogenesis is complete. Thus, once the initial hair is shed it does not regrow. VDR expression in the epidermal component of the hair follicle, the keratinocyte, is critical for maintenance of the hair cycle. To determine which functional domains of the VDR are required for hair cycling, mutant VDR transgenes were targeted to the keratinocytes of VDR null mice. Keratinocyte-specific expression of a VDR transgene with a mutation in the hormone binding domain that abolishes ligand binding restores normal hair cycling in VDR null mice, whereas a VDR transgene with a mutation in the AF2 domain that impairs nuclear receptor coactivator recruitment, results in a partial rescue.
Mutations in the nuclear receptor corepressor Hairless are also associated with alopecia in humans and mice. Hairless binds the VDR, resulting in transcriptional repression. Neither VDR mutation affects Hairless interactions or its ability to repress transcription. These studies demonstrate that the effects of the VDR on the hair follicle are ligand-independent and point to novel molecular and cellular actions of this nuclear receptor.
NURSA Molecule Pages Link:
This article has been cited by other articles:
 |
|
 |
|
  C. Gysemans, E. van Etten, L. Overbergh, A. Giulietti, G. Eelen, M. Waer, A. Verstuyf, R. Bouillon, and C. Mathieu Unaltered Diabetes Presentation in NOD Mice Lacking the Vitamin D Receptor Diabetes, January 1, 2008; 57(1): 269 - 275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Wang, P. J. Malloy, and D. Feldman Interactions of the Vitamin D Receptor with the Corepressor Hairless: ANALYSIS OF HAIRLESS MUTANTS IN ATRICHIA WITH PAPULAR LESIONS J. Biol. Chem., August 31, 2007; 282(35): 25231 - 25239. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Cianferotti, M. Cox, K. Skorija, and M. B. Demay Vitamin D receptor is essential for normal keratinocyte stem cell function PNAS, May 29, 2007; 104(22): 9428 - 9433. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
T. I. Ellison, R. L. Eckert, and P. N. MacDonald Evidence for 1,25-Dihydroxyvitamin D3-independent Transactivation by the Vitamin D Receptor: UNCOUPLING THE RECEPTOR AND LIGAND IN KERATINOCYTES J. Biol. Chem., April 13, 2007; 282(15): 10953 - 10962. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. M. Blumberg, I. Tzameli, I. Astapova, F. S. Lam, J. S. Flier, and A. N. Hollenberg Complex Role of the Vitamin D Receptor and Its Ligand in Adipogenesis in 3T3-L1 Cells J. Biol. Chem., April 21, 2006; 281(16): 11205 - 11213. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. DEMAY Mechanism of Vitamin D Receptor Action Ann. N.Y. Acad. Sci., April 1, 2006; 1068(1): 204 - 213. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Endocrinology | Endocrine Reviews | J. Clin. End. & Metab. |
| Molecular Endocrinology | Recent Prog. Horm. Res. | All Endocrine Journals |
