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Its Role in Calcium Homeostasis1How 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.

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To Make Me D, Warm Me Up and Hydroxylate Me..3X!4Vitamin DVitamin 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 NeedFunctions of Vitamin D in Calcium homeostasisFunctions 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 Site of Action of Vitamin D1,25(OH)2D helps to maintain calcium and phosphate in serum by its action on intestine, bone, kidney, and the parathyroidsIn small intestine, 1,25(OH)2D stimulates calcium absorption , primarily in duodenum and phosphate absorption by jejunum and ileumAt high concentrations, 1,25(OH)2D increases bone resorption In the kidneys, 1,25(OH)2D inhibits its own synthesis and stimulates its metabolism1,25(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

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], stimulates the synthesis of the epithelial calcium channels in the plasma membrane, calcium pumps , and

induces the formation of the calbindins. 11 Once joined with ingested vitamin D, facilitate increased serum calcium levels .

Shows Expressed Calbindins and How they facilitate transport of Calcium through the Membranes

12Calcium Absorption Enhanced by Carrier Protein Calbindin

13Calcium 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

14Vitamin D Actions on BonesAnother 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:Increases Ca++ absorption by the small intestine.

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)

16OPG--osteoprotegerinBut, 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.

18Vitamin D Mode of ActionVitamin 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 a-globulin.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 DWhen these signal molecules bind to their receptor proteins, they activate the receptors , which bind to DNA to regulate the transcription of specific genes

CALCITONINCalcitonin32 amino acidsC cells or the parafollicular cells of the thyroid glandActionInhibits bone resorptionDecrease blood calciumIncrease Na+, Ca++ and phosphate excretion in the urineDecrease gastric acid secretionAntagonist to PTHSites and mode of action:Acts on both bone and kidneyCalcitonin:Reduces plasma calcium in three waysDecrease the activity of the osteoclast Increase the osteoblastic activityPrevent formation of new osteoclast from osteoprogenitor cellsIncrease both urinary calcium and phosphate clearanceCalcitoninWhat happens.Action on bones:Calcitonin inhibits resorption of bones by osteoclasts; thus reduces mobilization of Ca and inorganic PO4 from bones into bloodStimulates influx of phosphates in bonesPromotion of bone formation is UNCERTAIN BUT it increases osteoblasts cellsCalcitoninAction on kidneys:Acts on distal tubule and ascending loop of Henle; Decreases tubular reabsorption of both calcium and inorganic phosphate PRODUCING calcinuria and phosphaturiaInhibits -1-hydroxylase and inhibits synthesis of Vit D3 thus decreasing calcium absorption from intestine

Mechanism of ActionRole of cyclic AMPCalcitonin 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 hormoneCellular shiftCalcitonin in vitro and in vivo produced a cellular shift in which the number of osteoclasts decreasedpH changeCalcitonin regulates pH at cellular level producing more alkaline medium which diminishes resorptionControl of calcitonin secretionRegulated by the extracellular concentration of ionized calcium.Elevated blood calcium levels strongly stimulate calcitonin secretionSecretion is suppressed when calcium concentration falls below normalEffect: lowers the circulating Ca++ and phosphate level