The vitamin D receptor functions as a transcription regulator in the absence of 1,25-dihydroxyvitamin D3

The Journal of Steroid Biochemistry and Molecular Biology
Seong Min Lee, J Wesley Pike

Abstract

The vitamin D receptor (VDR) is a critical mediator of the biological actions of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3). As a nuclear receptor, ligand activation of the VDR leads to the protein's binding to specific sites on the genome that results in the modulation of target gene expression. The VDR is also known to play a role in the hair cycle, an action that appears to be 1,25(OH)2D3-independent. Indeed, in the absence of the VDR as in hereditary 1,25-dihydroxyvitamin D resistant rickets (HVDRR) both skin defects and alopecia emerge. Recently, we generated a mouse model of HVDRR without alopecia wherein a mutant human VDR lacking 1,25(OH)2D3-binding activity was expressed in the absence of endogenous mouse VDR. While 1,25(OH)2D3 failed to induce gene expression in these mice, resulting in an extensive skeletal phenotype, the receptor was capable of restoring normal hair cycling. We also noted a level of secondary hyperparathyroidism that was much higher than that seen in the VDR null mouse and was associated with an exaggerated bone phenotype as well. This suggested that the VDR might play a role in parathyroid hormone (PTH) regulation independent of 1,25(OH)2D3. To evaluate this hypothesis further, we contrasted PTH levels...Continue Reading

Citations

Nov 12, 2019·Reproduction, Fertility, and Development·Xiaolei YaoPeihua You
Aug 28, 2016·Journal of Cellular Biochemistry·Sohel ShamsuzzamanJohn W Pike
May 3, 2018·Clinical Epigenetics·Daniel Castellano-CastilloManuel Macias-Gonzalez
Feb 28, 2017·The Journal of Clinical Investigation·J Wesley PikeNancy A Benkusky
Mar 5, 2017·Pediatrics International : Official Journal of the Japan Pediatric Society·Sule YesilGurses Sahin
Feb 8, 2020·Nature Reviews. Endocrinology·Daniel Bikle, Sylvia Christakos
Jan 26, 2021·Nutrition Reviews·Natalia Wawrzyniak, Joanna Suliburska
Feb 23, 2021·Case Reports in Dermatological Medicine·Sanusi Umar, Marissa J Carter

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