Genomic Action of Vitamin D

Genomic Action of Vitamin D

Overview

  • Lecture Title: Genomic action of Vitamin D and its receptor (NSC 408 Lecture 8.2)

  • Learning Objective (MLO 8.2): List the different steps of vitamin D synthesis and its genomic mechanism of action.

Vitamin D Synthesis and Mechanism of Action

  • Vitamin D Receptors:

    • Function similar to hormones (hormone-like properties).

  • Definitions:

    • Nuclear Hormone Receptors: A class of proteins that receive and transmit signals from steroid hormones.

    • Hormone Response Element (HRE): A specific sequence within the target gene that nuclear hormone receptors bind to regulate gene expression.

Genomic Mechanism of Vitamin D Action

  • Components Involved:

    • 1,25VD PO4 (1,25-dihydroxyvitamin D): The active form of Vitamin D.

    • VDR (Vitamin D Receptor):

    • Depicted in green in diagrams, it binds to vitamin D.

    • RXR (Retinoid-X-Receptor): A partner receptor for VDR that assists in forming the active receptor complex.

    • VDRE (VDR Responsive Elements): Specific DNA sequences that the VDR binds to in the promoter region of target genes.

Mechanisms of Vitamin D Action

  1. Repression Phase:

    • Inactive Vitamin D Nuclear Receptor:

      • Process: The inactive form interacts with corepressors leading to repression of basal transcription.

      • Location: Happens within the nuclear membrane.

  2. Activation Phase:

    • Active Vitamin D Nuclear Receptor:

      • Phosphorylation states observed in the receptor complex.

      • Coactivators:

      • SRC-1: Steroid Receptor Coactivator-1, promotes transcriptional activity.

      • CBP: CREB Binding Protein, acts as a coactivator for VDR.

      • Promoter Region: Engagement of the active complex at VDRE leads to activation of gene transcription.

Effects of 1,25(OH) D3

  • Biological Action:

    • Enhances calcium absorption in the intestines.

    • Target Gene: Calbindin, a calcium-binding protein crucial for calcium transport.

    • Outcome: Increased levels of 1,25(OH)D3 lead to an increase in calbindin mRNA, facilitating greater calcium uptake.

Calcium Absorption Process in Enterocytes

  • Processes:

    • Intestinal Brush Border: Site of calbindin action and calcium ion transport.

    • Transport Mechanisms:

    • Ca2+-Mg2+ ATPase: An enzyme present in the duodenum that aids in calcium transport.

    • Na-Ca2+ Exchange System: Mechanism operating primarily in the jejunum and ileum to facilitate calcium absorption.

    • Transport to Blood and Target Tissues: Resulting from enhanced calbindin and active transport mechanisms.

Visual Aids

  • Reference Figures provided in the material:

    • Figure 12.151: Illustration of nuclear hormone receptors action.

    • Figure 12.152: Depicting the Vitamin D receptor and the biochemical pathways involved in target gene action.

    • Figure 12.211: Visual representation of calcium uptake and absorption mechanisms in enterocytes.