Justify the statement 'Vitamin D is a hormone'. Describe the synthesis, mechanism of action and physiological functions of vitamin D.

Justification: Vitamin D as a Hormone

The classification of Vitamin D as a hormone is justified by several key characteristics:

• Synthesis Site: Unlike essential vitamins obtained solely from diet, Vitamin D can be synthesized endogenously in the skin upon exposure to ultraviolet B (UVB) radiation.
• Activation Pathway: Vitamin D undergoes a multi-step activation process involving the liver and kidneys, similar to the activation of steroid hormones.
• Receptor-Mediated Action: Vitamin D exerts its effects by binding to the Vitamin D Receptor (VDR), a nuclear receptor that forms a complex with retinoid X receptor (RXR). This complex then binds to Vitamin D Response Elements (VDREs) on DNA, regulating gene transcription.
• Systemic Effects: Vitamin D influences a wide range of physiological processes beyond calcium homeostasis, including immune function, cell growth, and differentiation.

Synthesis of Vitamin D

Vitamin D synthesis occurs through three main pathways:

• Cutaneous Synthesis: 7-dehydrocholesterol in the skin is converted to previtamin D3 upon exposure to UVB radiation. Previtamin D3 then isomerizes to Vitamin D3 (cholecalciferol). This is the primary source of Vitamin D.
• Dietary Intake: Vitamin D2 (ergocalciferol) is obtained from plant sources and fortified foods. Vitamin D3 is found in animal sources like fatty fish and egg yolks.
• Supplements: Vitamin D2 and D3 are available as dietary supplements.

Following synthesis or absorption, both Vitamin D2 and D3 are transported to the liver, where they are hydroxylated to 25-hydroxyvitamin D [25(OH)D], also known as calcidiol. This is the major circulating form of Vitamin D and is used to assess Vitamin D status. Calcidiol is then transported to the kidneys, where it undergoes a second hydroxylation to form 1,25-dihydroxyvitamin D [1,25(OH)2D], also known as calcitriol. Calcitriol is the biologically active form of Vitamin D.

Mechanism of Action

The mechanism of action of Vitamin D involves the following steps:

• Binding to VDR: Calcitriol enters target cells and binds to the VDR, located primarily in the nucleus.
• VDR-RXR Heterodimerization: The VDR forms a heterodimer with the retinoid X receptor (RXR).
• VDRE Binding: The VDR-RXR complex binds to specific DNA sequences called Vitamin D Response Elements (VDREs) located in the promoter regions of target genes.
• Gene Transcription: Binding to VDREs regulates the transcription of target genes, leading to altered protein synthesis and cellular function.

Vitamin D also exerts some rapid, non-genomic effects through intracellular calcium signaling pathways.

Physiological Functions of Vitamin D

Vitamin D plays a crucial role in numerous physiological processes:

• Calcium Homeostasis: Calcitriol increases intestinal calcium absorption, reduces calcium excretion by the kidneys, and promotes calcium mobilization from bone, maintaining serum calcium levels.
• Bone Health: Vitamin D is essential for bone mineralization and remodeling, preventing rickets in children and osteomalacia and osteoporosis in adults.
• Immune Modulation: Vitamin D enhances innate immunity and modulates adaptive immunity, reducing the risk of autoimmune diseases and infections.
• Cell Growth and Differentiation: Vitamin D regulates cell proliferation, differentiation, and apoptosis, potentially playing a role in cancer prevention.
• Cardiovascular Health: Vitamin D may contribute to cardiovascular health by regulating blood pressure and reducing inflammation.
• Neurological Function: Vitamin D receptors are present in the brain, and Vitamin D may play a role in cognitive function and neuroprotection.

Function	Mechanism
Calcium Absorption	Increases expression of calcium transport proteins in the intestine.
Bone Remodeling	Regulates osteoblast and osteoclast activity.
Immune Modulation	Enhances antimicrobial peptide production and modulates T cell function.