The Skin and Vitamin D

January 2012 in “ Human health handbooks ”

Daniel D. Bikle

vitamin D 7-dehydrocholesterol ultraviolet radiation keratinocytes vitamin D receptor VDR hair follicle cycle DRIP SRC hairless Hr β-catenin UV radiation vitamin D3

From the encyclopedia

Vitamin D →

vitamin you should probably be taking for general health might also help your hair a little

cholecalciferol →

Studysummary This review examines the various functions of vitamin D and its receptor in regulating skin processes, highlighting their role in cell differentiation, immunity, and tumor suppression, but reports no new clinical results. Our plain-language summary of this paper — not a Tressless recommendation.

The document reviewed the role of the skin as the primary source of vitamin D for the body, highlighting its ability to convert 7-dehydrocholesterol to vitamin D3 under ultraviolet radiation. It discussed the importance of vitamin D in regulating bone mineral homeostasis and various non-classical actions such as cell differentiation, hormone secretion, and immune function. The skin's keratinocytes were noted for their unique ability to metabolize vitamin D to its active form and respond to it via the vitamin D receptor (VDR). The review explored how vitamin D and VDR regulate skin functions, including cell proliferation, differentiation, immunity, hair follicle cycle regulation, and tumor suppression, with regulation involving coregulators like DRIP, SRC, hairless (Hr), and β-catenin.

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research Quantification of the Vitamin D Receptor-Coregulator Interaction

62 citations , January 2009 in “Biochemistry”

This study found that both the natural ligand 1alpha,25(OH)(2)D(3) and the synthetic agonist LG190178 bind similarly to the vitamin D receptor's coregulator motifs, suggesting similar biological functions.

research Vitamin D and Human Health: Lessons from Vitamin D Receptor Null Mice

1533 citations , October 2008 in “Endocrine reviews”

This research highlights that engineered mice lacking the vitamin D receptor show multiple health issues similar to human vitamin D deficiency, underscoring the widespread impacts of the vitamin D endocrine system.

research Inactivation of the Vitamin D Receptor Enhances Susceptibility of Murine Skin to UV-Induced Tumorigenesis

148 citations , May 2008 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that mice lacking the vitamin D receptor (VDR) developed skin tumors more rapidly than those with normal VDR activity, regardless of 1,25-dihydroxyvitamin D(3) presence.

research The Vitamin D Receptor Is a Wnt Effector That Controls Hair Follicle Differentiation and Specifies Tumor Type in Adult Epidermis

127 citations , January 2008 in “PloS one”

This study observed that the vitamin D receptor is crucial for hair follicle formation and altering tumor development in the Wnt signaling pathway, suggesting therapeutic potential for vitamin D analogues in related tumors.

research Vitamin D Receptor Is Essential For Normal Keratinocyte Stem Cell Function

143 citations , May 2007 in “Proceedings of the National Academy of Sciences”

This study found that absence of the vitamin D receptor in keratinocytes impairs canonical Wnt signaling and leads to alopecia due to defects in keratinocyte stem cells.

research Development and Progression of Alopecia in the Vitamin D Receptor Null Mouse

81 citations , January 2006 in “Journal of cellular physiology”

This study found that the absence of the vitamin D receptor disrupts hair follicle structure during the first catagen in mice, linked to increased expression of the hairless gene.

research Hairless Suppresses Vitamin D Receptor Transactivation in Human Keratinocytes

78 citations , November 2005 in “Endocrinology”

This study found that Hairless (Hr) acts as a corepressor of the vitamin D receptor (VDR) in human keratinocytes, blocking the action of vitamin D on keratinocyte differentiation.

research FOXE1, A New Transcriptional Target Of GLI2, Is Expressed In Human Epidermis And Basal Cell Carcinoma

92 citations , May 2004 in “Journal of Investigative Dermatology”

research Physical And Functional Interaction Between The Vitamin D Receptor And Hairless Corepressor, Two Proteins Required For Hair Cycling

215 citations , September 2003 in “Journal of Biological Chemistry”

This study found that the hairless gene product (Hr) suppresses VDR-mediated gene activation by directly interacting with the vitamin D receptor, potentially affecting hair follicle function.

research K6irs1, K6irs2, K6irs3, And K6irs4 Represent The Inner-Root-Sheath-Specific Type II Epithelial Keratins Of The Human Hair Follicle

130 citations , April 2003 in “Journal of Investigative Dermatology”

This study reports the cloning and expression details of two new human type II keratins, K6irs3 and K6irs4, in the hair follicle's inner root sheath, suggesting a distinct functional role related to hair structure.

Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

research Targeted Expression of Human Vitamin D Receptor in the Skin Promotes the Initiation of the Postnatal Hair Follicle Cycle and Rescues Alopecia in Vitamin D Receptor Null Mice

57 citations , April 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study found that the vitamin D receptor is crucial for initiating the postnatal hair follicular cycle in mice, preventing alopecia associated with its inactivation.

research Lack of the Vitamin D Receptor Is Associated with Reduced Epidermal Differentiation and Hair Follicle Growth

180 citations , January 2002 in “The journal of investigative dermatology/Journal of investigative dermatology”

This study observed that vitamin D receptor knockout mice exhibit impaired epidermal differentiation and progressive hair loss, suggesting the importance of the vitamin D receptor in normal skin and hair follicle development.

research Targeting Expression of the Human Vitamin D Receptor to the Keratinocytes of Vitamin D Receptor Null Mice Prevents Alopecia

115 citations , December 2001 in “Endocrinology”

This study found that restoring vitamin D receptor expression specifically in the keratinocytes of VDR null mice prevented alopecia and enhanced hair follicle response during anagen initiation.

research Atrichia Caused by Mutations in the Vitamin D Receptor Gene Is a Phenocopy of Generalized Atrichia Caused by Mutations in the Hairless Gene

139 citations , September 2001 in “The journal of investigative dermatology/Journal of investigative dermatology”

This case report describes a patient with mutations in both alleles of the vitamin D receptor who exhibited hair loss clinically indistinguishable from generalized atrichia with papules, suggesting a potential genetic pathway shared with the hairless gene.

research Extrarenal Expression of 25-Hydroxyvitamin D3-1α-Hydroxylase

845 citations , February 2001 in “The Journal of Clinical Endocrinology & Metabolism”

This study identified the presence of the enzyme 1 alpha-hydroxylase in various extrarenal tissues, suggesting its potential role in modulating vitamin D function in peripheral tissues.

research Evaluation of Keratinocyte Proliferation and Differentiation in Vitamin D Receptor Knockout Mice

114 citations , June 2000 in “Endocrinology”

In this study, the researchers found that alopecia in VDR null mice is likely due to issues with hair cycle initiation rather than defects in keratinocyte proliferation or differentiation.

research Induction of Basal Cell Carcinomas and Trichoepitheliomas in Mice Overexpressing GLI-1

380 citations , March 2000 in “Proceedings of the National Academy of Sciences”

This study demonstrates that mice with ectopic expression of the human GLI-1 gene in their skin developed tumors resembling human basal cell carcinoma, suggesting that GLI-1 is central to tumor development without additional p53 or Ha ras mutations.

research The Role of the Hairless (Hr) Gene in the Regulation of Hair Follicle Catagen Transformation

166 citations , July 1999 in “American Journal Of Pathology”

This study found that the loss of a functional hr gene in mice leads to premature and abnormal hair follicle regression, disrupting normal hair cycling and architecture.

research Normalization of Mineral Ion Homeostasis by Dietary Means Prevents Hyperparathyroidism, Rickets, and Osteomalacia, But Not Alopecia in Vitamin D Receptor-Ablated Mice

519 citations , October 1998 in “Endocrinology”

The study found that normalizing mineral ion levels in vitamin D receptor-ablated mice prevented hyperparathyroidism and bone disorders but did not address hair loss, indicating the VDR's role in hair growth.

research Alopecia Universalis Associated With a Mutation in the Human Hairless Gene

412 citations , January 1998 in “Science”

This study identified a missense mutation in the human hairless gene associated with a rare form of recessively inherited alopecia universalis, pinpointed on chromosome 8p12.

research Analysis of the Relation Between Alopecia and Resistance to 1,25-Dihydroxyvitamin D

100 citations , October 1986 in “Clinical Endocrinology”

This study found that alopecia in hereditary resistance to 1,25(OH)2D may indicate a more severe form of the condition, associated with earlier diagnosis and different responses to calciferol therapy.

research Calcitriol-Resistant Rickets With Alopecia

55 citations , May 1985 in “Archives of Dermatology”

This study found that alopecia in four children was linked to severe calcitriol-resistant rickets, suggesting this condition should be considered among inherited hair growth disorders.

research Topographical and Developmental Studies on Target Sites of 1,25 (OH)₂ Vitamin D₃ in Skin

70 citations , November 1984 in “Cell & tissue research/Cell and tissue research”

Vitamin D3 affects cell differentiation in specific skin areas.