Cell Signaling Pathways: Steroid Hormones (Vitamin D3) Flashcards
What are some sources of Vitamin D?
-sun exposure 5-10 minutes 2-3 times per week (longer if you live further north)
-cod liver oil
-mackerel
-trout
-salmon
-oysters
Can vitamin D deficiency lead to caries?
possibly
vitamin D can:
-produces cathelicidin and defensins
-antibacterial effects
-reduce bacteria that are able to create acid that break down enamel
What is the biologically active form of vitamin D3?
calcitrol 1alpha,25 (OH)2D3
Where is a majority of the biologically active D3 made?
kidney
-skin and some immune cells can also make some for autocrine or paracrine mechanism
what kind of hormone is circulating vitamin D3 considered?
endocrine
What is checked for in blood test to determine D3 concentration?
25(OH)D3
How is 25(OH)D3 transported in the blood?
by vitamin D binding protein
-member of albumin family
Is the receptor affinity high or low for 1,25(OH)2D3?
very high, allows even low amount of bind
What happens to VDR after1,25(OH)2D3 binds?
form heterodimeric complex with other nuclear hormone receptors (retinoid X receptor; RXR)
-this binds to DNA promoter containing VDRE
-recruit proteins needed for transcription
What does 1,25(OH)2D3 do to calcium concentration in gut?
allows for more Ca2+ uptake on apical side which allows it to be pumped out of the basal side into the capillary
What turns 7-dehydrocholesterol into Previtamin D3?
UVB
Main circulating form of Vitamin D?
25(OH)D3
Cholecalciferol
Where is 7-dehydrochesterol made?
in the skin in response to light
Steps to produce Vitamin D3 in the body:
Provitamin D3 (7-dehydrocholesterol) in skin
-convert to Previtamin D3 by UVB
-convert to Vitamin D3 by thermal isomerization
-convert to 25(OH)D3 in the liver by 25-hydroxylase
-convert to 1alpha25(OH)2D3 in kidney by 1alpha hydroxylase
What is ergocalciferol?
vitamin D2, most common in fortified foods
-less potent and shorter acting
What is the vitamin D receptor?
transcription factor
-nuclear hormone receptor
What is the name of the sequence that the vitamin D receptor binds to on DNA promoter sequence?
VRDE
vitamin D receptor element
What happens when the vitamin D receptor binds to VDRE?
recruits in bringing in regulatory elements that will stimulate or inhibit transcription
What is the main function of 1,25 (OH2) D3?
increase calcium uptake in the gut
Movement of Calcium across gut cells:
1,25(OH2)D3 enters the cell
-calcium binds to calbindin and transport to basal side
-CaATPase pump calcium out of the basal side of cell
Vitamin D receptor regulated genes
-genes expressed in osteoblasts needed to form bones
-induce expression of RANKL
-anti-microbial peptide made in salivary gland and mucosal eptihelium
What is a severe Vitamin D3 deficieny?
Rickets
Roles of vitamin D3
-calcium and phosphate homeostasis
-play roles muscle and immune function
-development of strong bones and teeth
Normal levels of calcium
above 30ng/ml
deficient levels of calcium
below 20 ng/ml
insufficient levels of calcium
20-29 ng/ml
percentage of people with vitamin D insufficiency and deficiency?
as high as 85%
What is rickets?
deficiency of vitamin D in growing children
What is the main source of Vitamin D in foods?
fish oil and fortification
What is the severe deficiency of vitamin D in adults?
osteomalacia
Symptoms of rickets and osteomalacia:
impaired bone mineralization and effect endochondral growth plates
-deformities in back
-leg bowing
-delayed eruption of permanent dentition
VDDR Type I (pseudovitamin D3 deficiency rickets)
-manifest by age 2
-defect in renal 25(OH) vitamin D 1alpha-hydrolase
-low circulating 1,25 (OH)2D3
-treat with massive doses of vitamin D3
VDDR Type II (hereditary vitamin D resistant rickets)
-normal at birth
defect in Vit D receptor (VDR)
-normal circulating amounts
-treat with high doses to try and saturate the receptors or with calcium
What is osteomalacia?
softening of the bones due to inadequate levels of calcium and phosphate
Oral manifestations of rickets:
abnormal dentin and enamel
-delayed eruption
-misalignment of teeth in jaw
-high caries index
-enamel hypoplasia
Amino acid mutations of vitamin D receptors cause what?
Vitamin D dependent rickets type II
All of those with mutation in DNA binding domain of VDDR Type II receptor also have:
alopecia
What is psoriasis?
immune mediated disease affecting skin that can be helped with vitamin D
How does vitamin D help psoriasis?
inhibit skin proliferation
What senses calcium serum levels?
calcium sensing receptor (CaSR) in parathyroid gland
What increases serum Ca2+ levels?
PTH (parathyroid hormone)
What decreases serum Ca2+ levels?
calcitonin (CT)
what mediates the actions of PTH on intestinal uptake of Ca and phosphate?
active vitamin D3
What does PTH do in kidneys?
increases phosphate excretion in urine
which form of calcium is physiologically active?
ionized calcium
Ionized calcium levels in serum?
4.4-5.4 mg/dl
serum total calcium
8.5-10.5 mg/dl
phosphate serum levels
2.5-4.5 mg/dl
magnisium serum levels
1.7-2.5 mg/dl
What is an early sign of low serum calcium?
oral tingling sensation in and around the mouth and lips
Generally, what is the only time we see hypophosphatemia?
malnutrition
-possibly in alcoholics and if there is increase secretions
Where is parathyroid hormone made?
parathyroid gland
What is the function of parathyroid hormone?
maintain concentration of calcium in the serum and extracellular fluid
What are the two PTH receptors?
PTH1R and PTHR2
What PTH receptor is involved in Calcium homeostasis?
PTH1R
What is PTHrP?
parathyroid hormone related peptide
-homolog to PTH, but does not stimulate 1,25(OH)2D3 in kidney
What is CaSR?
calcium sensing receptor
-regulate PTH secretion in parathyroid
-G-protein coupled receptor
-mutations can cause disorder is calcium homeostasis
What does IP3 do to PTH release?
inhibit
What does cAMP do to PTH release?
stimulate
Signaling when calcium is high in the blood:
IP3 signals PTH to not be released
-decrease release from bones
-decrease uptake in gut
-decrease reabsorption in kidney
Signaling when calcium is low in the blood :
cAMP signals PTH to be released
-increase release from bones
-increase uptake in gut
-increase reabsorption in kidney
Normal 25-OH-vitamin D levels are considered to be what value?
> 30ng/ml
