Cell Signaling Pathways: Steroid Hormones (Vitamin D3) Flashcards

1
Q

What are some sources of Vitamin D?

A

-sun exposure 5-10 minutes 2-3 times per week (longer if you live further north)
-cod liver oil
-mackerel
-trout
-salmon
-oysters

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2
Q

Can vitamin D deficiency lead to caries?

A

possibly
vitamin D can:
-produces cathelicidin and defensins
-antibacterial effects
-reduce bacteria that are able to create acid that break down enamel

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3
Q

What is the biologically active form of vitamin D3?

A

calcitrol 1alpha,25 (OH)2D3

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4
Q

Where is a majority of the biologically active D3 made?

A

kidney
-skin and some immune cells can also make some for autocrine or paracrine mechanism

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5
Q

what kind of hormone is circulating vitamin D3 considered?

A

endocrine

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6
Q

What is checked for in blood test to determine D3 concentration?

A

25(OH)D3

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7
Q

How is 25(OH)D3 transported in the blood?

A

by vitamin D binding protein
-member of albumin family

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8
Q

Is the receptor affinity high or low for 1,25(OH)2D3?

A

very high, allows even low amount of bind

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9
Q

What happens to VDR after1,25(OH)2D3 binds?

A

form heterodimeric complex with other nuclear hormone receptors (retinoid X receptor; RXR)
-this binds to DNA promoter containing VDRE
-recruit proteins needed for transcription

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10
Q

What does 1,25(OH)2D3 do to calcium concentration in gut?

A

allows for more Ca2+ uptake on apical side which allows it to be pumped out of the basal side into the capillary

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11
Q

What turns 7-dehydrocholesterol into Previtamin D3?

A

UVB

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12
Q

Main circulating form of Vitamin D?

A

25(OH)D3
Cholecalciferol

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13
Q

Where is 7-dehydrochesterol made?

A

in the skin in response to light

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14
Q

Steps to produce Vitamin D3 in the body:

A

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

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15
Q

What is ergocalciferol?

A

vitamin D2, most common in fortified foods
-less potent and shorter acting

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16
Q

What is the vitamin D receptor?

A

transcription factor
-nuclear hormone receptor

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17
Q

What is the name of the sequence that the vitamin D receptor binds to on DNA promoter sequence?

A

VRDE
vitamin D receptor element

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18
Q

What happens when the vitamin D receptor binds to VDRE?

A

recruits in bringing in regulatory elements that will stimulate or inhibit transcription

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19
Q

What is the main function of 1,25 (OH2) D3?

A

increase calcium uptake in the gut

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20
Q

Movement of Calcium across gut cells:

A

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

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21
Q

Vitamin D receptor regulated genes

A

-genes expressed in osteoblasts needed to form bones
-induce expression of RANKL
-anti-microbial peptide made in salivary gland and mucosal eptihelium

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22
Q

What is a severe Vitamin D3 deficieny?

A

Rickets

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23
Q

Roles of vitamin D3

A

-calcium and phosphate homeostasis
-play roles muscle and immune function
-development of strong bones and teeth

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24
Q

Normal levels of calcium

A

above 30ng/ml

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25
Q

deficient levels of calcium

A

below 20 ng/ml

26
Q

insufficient levels of calcium

A

20-29 ng/ml

27
Q

percentage of people with vitamin D insufficiency and deficiency?

A

as high as 85%

28
Q

What is rickets?

A

deficiency of vitamin D in growing children

29
Q

What is the main source of Vitamin D in foods?

A

fish oil and fortification

30
Q

What is the severe deficiency of vitamin D in adults?

A

osteomalacia

31
Q

Symptoms of rickets and osteomalacia:

A

impaired bone mineralization and effect endochondral growth plates
-deformities in back
-leg bowing
-delayed eruption of permanent dentition

32
Q

VDDR Type I (pseudovitamin D3 deficiency rickets)

A

-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

33
Q

VDDR Type II (hereditary vitamin D resistant rickets)

A

-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

34
Q

What is osteomalacia?

A

softening of the bones due to inadequate levels of calcium and phosphate

35
Q

Oral manifestations of rickets:

A

abnormal dentin and enamel
-delayed eruption
-misalignment of teeth in jaw
-high caries index
-enamel hypoplasia

36
Q

Amino acid mutations of vitamin D receptors cause what?

A

Vitamin D dependent rickets type II

37
Q

All of those with mutation in DNA binding domain of VDDR Type II receptor also have:

A

alopecia

38
Q

What is psoriasis?

A

immune mediated disease affecting skin that can be helped with vitamin D

39
Q

How does vitamin D help psoriasis?

A

inhibit skin proliferation

40
Q

What senses calcium serum levels?

A

calcium sensing receptor (CaSR) in parathyroid gland

41
Q

What increases serum Ca2+ levels?

A

PTH (parathyroid hormone)

42
Q

What decreases serum Ca2+ levels?

A

calcitonin (CT)

43
Q

what mediates the actions of PTH on intestinal uptake of Ca and phosphate?

A

active vitamin D3

44
Q

What does PTH do in kidneys?

A

increases phosphate excretion in urine

45
Q

which form of calcium is physiologically active?

A

ionized calcium

46
Q

Ionized calcium levels in serum?

A

4.4-5.4 mg/dl

47
Q

serum total calcium

A

8.5-10.5 mg/dl

48
Q

phosphate serum levels

A

2.5-4.5 mg/dl

49
Q

magnisium serum levels

A

1.7-2.5 mg/dl

50
Q

What is an early sign of low serum calcium?

A

oral tingling sensation in and around the mouth and lips

51
Q

Generally, what is the only time we see hypophosphatemia?

A

malnutrition
-possibly in alcoholics and if there is increase secretions

52
Q

Where is parathyroid hormone made?

A

parathyroid gland

53
Q

What is the function of parathyroid hormone?

A

maintain concentration of calcium in the serum and extracellular fluid

54
Q

What are the two PTH receptors?

A

PTH1R and PTHR2

55
Q

What PTH receptor is involved in Calcium homeostasis?

A

PTH1R

56
Q

What is PTHrP?

A

parathyroid hormone related peptide
-homolog to PTH, but does not stimulate 1,25(OH)2D3 in kidney

57
Q

What is CaSR?

A

calcium sensing receptor
-regulate PTH secretion in parathyroid
-G-protein coupled receptor
-mutations can cause disorder is calcium homeostasis

58
Q

What does IP3 do to PTH release?

A

inhibit

59
Q

What does cAMP do to PTH release?

A

stimulate

60
Q

Signaling when calcium is high in the blood:

A

IP3 signals PTH to not be released
-decrease release from bones
-decrease uptake in gut
-decrease reabsorption in kidney

61
Q

Signaling when calcium is low in the blood :

A

cAMP signals PTH to be released
-increase release from bones
-increase uptake in gut
-increase reabsorption in kidney

62
Q

Normal 25-OH-vitamin D levels are considered to be what value?

A

> 30ng/ml