HORMON PARATIROID

( PTH )
DISINTESIS DALAM BENTUK TIDAK AKTIF

PREPROHORMON RIBOSOM

PROHORMON ENDOPLASMIK RETIKULUM

HORMON AKTIF APARATUS GOLGI

. PTH synthesized as a 115-aa polypeptide
cleaved to pro-PTH (90-aa)  PTH (84-
aa)
• Intact PTH: The major storage, secreted,
and biologically active form of the hormone
• Biosynthetic process takes less than one
hour
• Within seconds after hypocalcemia  PTH
1-84 secreted by exocytosis
• Calcium regulates release, synthesis and
degradation of PTH .PTH gene is located in
chromosome 11
 Parathyroid hormone
• 84 amino peptide
• Molecular mass of 9.6 kilodalton
• Full biologic activity resides in the amino
terminal third of the molecule
• PTH 1-34 has full biologic activity while
region 25-34 is for receptor binding
Parathyroid Hormone
 Experiment

Plasma Ca+2
concentration

PO4-3

inject PTH here

Time
 PARATHORMONE
HORMON MENGIKAT RESEPTOR
DI TRANSMEMBRAN / PERMUKAAN
SEL DENGAN MENGGUNAKAN
MEDIATOR : c AMP
 α
βγ
αs-GTP + βγ αsβγ-GTP
GTP ase

αsβγ-GDP
1
 Vitamin D dan hormon paratiroid

• Produksi awal vitamin D

– ergosterol tanaman: radiasi UV  D2/D3
– kulit: 7‑dehidrokolesterol U V  D3
• Perubahan di hati: D3  25-OH D3 ( 25 OH ase )
• Perubahan di ginjal: 25-OH D3  1 OH ase
– 1,25-(OH)2-D3: potensi 10x D3 ( Pengaruh PTH )
– 24,25-(OH)2-D3: potensi 0,5x D3
 Half life of PTH is 2-4 minutes
The biologic activity of PTH resides
in its amino terminus
The effect of PTH are initiated by
binding of PTH to PTH receptors in
target tissues ( type I )
Type 2 receptors have been found in
brain and intestines ( function unknown )
Regulation of PTH release by Plasma
Ca2+ Levels
• PTH is released by chief cells in the
parathyroid gland.
• Chief cells contain receptors for Ca2+
• A decrease in plasma Ca2+ levels
mediates the release of PTH . Ca²+
does not bind to receptor .
• Conversely, hypercalcemia inhibits PTH
release . Ca 2+ binds to receptor .
Calcium Receptor
 REGULASI
PTH
1. REGULASI SINTESIS

2. REGULASI METABOLISME
1.REGULASI SINTESIS dikaitkan

dengan degradasi proPTH

2. REGULASI METABOLISME
dikaitkan
dengan degradasi PTH

3. REGULASI SEKRESI dikaitkan

dengan sekresi PTH
 PTH

• Regulation of Synthesis
– Biosynthesis is regulated by levels of calcium
– An acute decrease of Ca results in marked increase of PTH mRNA
increase of PTH synthesis as a result of the pro PTH degradation
– Effects is at the level of gene transciption, mRNA stability, mRNA
translation
– Rate of degradation of PTH is low if low calcium and high if calcium is
high ( regulation of metabolism )
– 1, 25 (OH)2D3 receptor complex binds with vitamin D in the promoter
region of PTH gene and inhibits transcription decreases the
production of PTH ( via nVDRE )
– PTH synthesis can be enhanced by the size and number of PTH
producing chief cells in cases of prolonged hypocalcemia
 Calcium and Hormonal
Regulators
• Calcium
• Calcitonin (CT )
Lowers Ca++ in the blood and inhibits osteoclasts
• Parathormone (PTH)
– Increases Ca++ in the blood
– Stimulates osteoclasts
• 1,25 Vitamin D3
– Increases Ca++ in the blood
– Increase Ca++ uptake from the gut
– Stimulates osteoclasts
 Other hormones affecting Ca
concentration and bone
development:
. Estrogens: promote bone growth. When
estrogens are reduced at menopause,
osteoporosis is accelerated.
• Testosterone: stimulates bone and cartilage
growth
• Growth hormone: promotes bone and
cartilage growth and increases intestinal
absorption of Ca
 PTH MERANGSANG
EKSKRESI BIKARBONAT DI
URINE SEHINGGA MUDAH
TERJADI PELEPASAN ION
KALSIUM DARI ALBUMIN
DITUBUH SEHINGGA
KALSIUM MUDA DIGUNAKAN
Effects of Calcitonin and Parathyroid Hormones
on Blood Calcium Levels

Para follicular cell / C cell ( Thyroid)

 1,25 Vitamin D3 sintesis : calcium binding
protein
• Increases Ca++ uptake from the gut
– Increase transcription and translation of Ca++ transport proteins in gut epithelium
• Minor roll: also stimulates osteoclasts UV
– Increase Ca++ resorption from the bone
Cholesterol precursor 7-dehydrocholesterol

Vitamin D3

25 OH Vitamin D3 ( 25 OH ase )

1,25 ( OH )2 Vitamin D3 ( 1 OH ase )

Low plasma Ca++ increase

kidney enzymes
 HORMONAL REGULATION
kidney
1,25 Vit. D3 (+)
Parathormone (+)
Calcitonin (-) Blood
resorption Ca++
deposition
PTH
Ca++

1,25 Vit D3 Ca++ lost in Calcitonin

intake urine

Ca++ in EXCRETION
the diet Ca++ lost in
small intestine feces
 Hidroksi ( OH ) prolin

katabolisme kollagen PTH

atau
sintesis kollagen GH

Bio assay dari GH untuk OH prolin

 PSEUDO
HIPERPARATIROIDISME
1. Kadar PTH : Normal
2. Reseptor menurun
3. Protein G menurun
4. Alur setelah pembentukan
cAMP menurun