Its Role in Calcium Homeostasis

How Does D Compare To Hormones? Vitamin D3 is not secreted by a classical endocrine gland, the active form of the hormone is released from the kidney and acts at distant sites or locally. Each of the forms of vitamin D is hydrophobic, and is transported in blood bound to carrier proteins.

To Make Me D, Warm Me Up and Hydroxylate Me..3X!

Vitamin D
Vitamin D, after its activation to the hormone 1,25-dihydroxy Vitamin D3 is a principal regulator of Ca++. Vitamin D increases Ca++ absorption from the intestine and Ca++ resorption from the bone as well as bone mineralization.

So..Exposure to Sun and Then, Fortified Foods.Give Us the D We Need

Functions of Vitamin D in Calcium homeostasis

Functions as a hormone to maintain blood calcium within normal range:
Enhances intestinal absorption of calcium and phosphorus. Promotes renal calcium retention. Mobilizes calcium from bone (resorption) as needed. Promotes bone mineralization.
Holick MF, 1996

 1,25(OH)2D helps to maintain calcium and phosphate in serum by its action on intestine, bone, kidney, and the parathyroids In small intestine, 1,25(OH)2D stimulates calcium absorption , primarily in duodenum and phosphate absorption by jejunum and ileum At high concentrations, 1,25(OH)2D increases bone resorption In the kidneys, 1,25(OH)2D inhibits its own synthesis and stimulates its metabolism 1,25(OH)2D acts directly on the parathyroids to inhibit the synthesis and secretion of PTH 1,25(OH)2D exerts its action by associating with a specific nuclear vit D receptor analogous to steroid receptors

Site of Action of Vitamin D

How Does Vitamin D Facilitate Calcium Absorption in the Intestines??

IN THE INTESTINE
It facilitates intestinal absorption of calcium, as well as stimulates absorption of phosphate and magnesium ions. In the absence of vitamin D, dietary calcium is not absorbed at all efficiently. Vitamin D stimulates the expression of a number of proteins involved in transporting calcium from the lumen of the intestine, across the epithelial cells and into blood.

The vitamin D form 1,25-dihydroxycholecalciferol [1,25(OH)2D3],

1. stimulates the synthesis of the epithelial calcium channels in the plasma membrane, calcium pumps , and 2. induces the formation of the calbindins.

Once joined with ingested vitamin D, facilitate increased serum calcium levels . Shows Expressed Calbindins and How they facilitate transport of Calcium through the Membranes

Calcium Absorption Enhanced by Carrier Protein Calbindin

Calcium absorption is a transport across the epithelial cell, which is greatly enhanced by the carrier protein calbindin, the synthesis of which is totally dependent on vitamin D

Vitamin D Actions on Bones

Another important target for 1,25-(OH)2-D is the bone. Osteoblasts, but not osteoclasts have vitamin D receptors. 1,25-(OH)2-D acts on osteoblasts which produce a paracrine signal that activates osteoclasts to resorb Ca++ from the bone matrix. 1,25-(OH)2-D also stimulates osteocytic osteolysis.

Calcitriol Raises Blood Calcium in 3 Ways:

1. Increases Ca++ absorption by the small intestine. 2. Increases Calcium (and Phosphate ) resorption from the skeleton. It binds to hematopoietic stem cells and causes differentiation of osteoclasts. 3. Weakly promotes the reabsorption of Calcium ions by the kidney cells (less calcium excreted)

But, I thought Vitamin D HELPED US retain Calcium?

Yes, It does. So, although there is some proliferation of osteoclasts, the NET RESULT IS: CALCIUM ABSORPTION and REMODELING.Outweighs RESORPTION. Because

Vitamin D has also been shown to play an important part in regulating the

proliferation and differentiation of both types of bone remodeling cells - those responsible for bone breakdown and those that reform the bone a newand more.

Vitamin D Mode of Action Vitamin D is a lipid soluble hormone that binds to a typical nuclear receptor, analogous to steroid hormones. Because it is lipid soluble, it travels in the blood bound to hydroxylated aglobulin. There are many target genes for Vitamin D.

Mode of Action of Vit D

 Small hydrophobic signal molecules diffuse directly across the plasma membrane of target cells and bind to intracellular receptor proteins, eg. Steroid hormones, thyroid hormones, retinoids and vitamin D When these signal molecules bind to their receptor proteins, they activate the receptors , which bind to DNA to regulate the transcription of specific genes

CALCITONIN

Calcitonin
32 amino acids C cells or the parafollicular cells of the thyroid gland Action
Inhibits bone resorption Decrease blood calcium Increase Na+, Ca++ and phosphate excretion in the urine Decrease gastric acid secretion

Antagonist to PTH

Sites and mode of action:

Acts on both bone and kidney Calcitonin:
Reduces plasma calcium in three ways
1. Decrease the activity of the osteoclast 2. Increase the osteoblastic activity 3. Prevent formation of new osteoclast from osteoprogenitor cells

Increase both urinary calcium and phosphate clearance

Calcitonin
What happens. 1. Action on bones:
Calcitonin inhibits resorption of bones by osteoclasts; thus reduces mobilization of Ca and inorganic PO4 from bones into blood Stimulates influx of phosphates in bones Promotion of bone formation is UNCERTAIN BUT it increases osteoblasts cells

Calcitonin
2. Action on kidneys:
Acts on distal tubule and ascending loop of Henle; Decreases tubular reabsorption of both calcium and inorganic phosphate PRODUCING calcinuria and phosphaturia Inhibits -1-hydroxylase and inhibits synthesis of Vit D3 thus decreasing calcium absorption from intestine

Mechanism of Action
1. Role of cyclic AMP
Calcitonin binds to specific calcitonin receptors on the plasma membrane of bone osteoclasts and renal tubular epithelial cells activates adenyl cyclase which increases cAMP which mediates the cellular effects of hormone

2. Cellular shift
Calcitonin in vitro and in vivo produced a cellular shift in which the number of osteoclasts decreased

3. pH change
Calcitonin regulates pH at cellular level producing more alkaline medium which diminishes resorption

Control of calcitonin secretion

Regulated by the extracellular concentration of ionized calcium. Elevated blood calcium levels strongly stimulate calcitonin secretion Secretion is suppressed when calcium concentration falls below normal Effect: lowers the circulating Ca++ and phosphate level