TOTAL ParaThyroid Hormone Synthesis,Storge Secretion and Transportation INFORMATION

1.  Hormone: A chemical
substance produced in the
body that controls and
regulates the activity of
certain cells or organs.
Many Hormones aresecretd
by special glands
 Hormones are the body's
chemical messengers and
are part of the Endocrine
system.
4/5/2018 Parathyroid Hormones 2

2. Hormone class Components Exmples
Amine Hormone Amiino acids with modified
groups
Adrenailne , thyroxin
Proteine Hormone Long chian of linked Amino
acids
ADH , insulin
Steroid Hormone Derived from the lipid
cholesterol
Cortisol,aldosterone,
estrogen
Peptide Hormone Short chian of linked
Amino acids
Glucagon ,prolactin ,ACTH
Parathyroide Hormone
4/5/2018 Parathyroid Hormones 3

3.  Parathyroid hormone is secreted
from four parathyroid glands, which
are small glands in the neck, located
behind the thyroid gland
 Parathyroid Hormones is secreted by
the chief cells of the parathyroid
glands as polypeptide containg 84
amino acids .
 It acts to increase the concentration
of calcium (Ca2+) in the blood.
 is important in bone remodeling,
which is an ongoing process in
which bone tissue is
alternately resorbed & rebuilt over
time.4/5/2018
Parathyroid Hormones
4

4. Parathyroid hormone regulates calcium levels in the
blood, largely by increasing the levels when they
are too low. It does this through its actions on
the kidneys, bones and intestine:
• Bones – parathyroid hormone stimulates the
release of calcium from large calcium stores in the
bones into the bloodstream. This increases bone
destruction and decreases the formation of new
bone.
• Kidneys – parathyroid hormone reduces loss of
calcium in urine. Parathyroid hormone also
stimulates the production of active vitamin D in the
kidneys.
• Intestine – parathyroid hormone indirectly
increases calcium absorption from food in the
intestine, via its effects on vitaminD metabolism.
4/5/2018 Parathyroid Hormones 5

5. 4/5/2018
Parathyroid Hormones 6

6. • Serum PTH concentrations are dependent
upon the release of PTH stored in
secretory granules within the parathyroid
gland and by the synthesis of new
PTH.Ca2+, phosphorus, and vitamin D
metabolites play a role in regulating PTH
release and synthesis
4/5/2018 Parathyroid Hormones 7

7. • Parathyroid hormone (PTH) is a polypeptide of 84 amino
acids that is synthesized and secreted by the parathyroid
glands . The hormone acts on the target organs, bone and
kidney, to promote the flow of calcium into the
extracellular fluid .
• The secretion of PTH, in turn, is regulated by the
concentrations of calcium in blood and extracellular
fluid, thus maintaining calcium homeostasis . In our
studies of the factors controlling the synthesis and
release of PTH, we identified a biosynthetic pathway for
the hormone that involves its formation via two
sequential proteolytic cleavages from a larger
biosynthetic precursor . The initial product synthesized
in parathyroid gland slices in vitro or by translation of
parathyroid gland mRNA in cell free systems is pre-
propara thyroid hormone (Pre-ProPTH) of 115 amino
acids .
• This initial prehormone, either during growth of the
nascent chain or within I min of completion of synthesis,
is converted to an intermediate precursor, proparathyroid
hormone (ProPTH) of 90 amino acids, by removal of the
amino-terminal sequence of 25 amino acids. After a
delay of -15 min, ProPTH undergoes a second
proteolytic cleavage, resulting in the removal of the
amino-terminal sequence of six amino acids, with the
resultant formation of PTH,the major hormonal product
stored in and secreted from the parathyroid gland
4/5/2018 Parathyroid Hormones 8

8. • The biosynthesis of precursor and
secretory forms of parathyroid hormone
(PTH). Within the nucleus, transcription
of the gene encoding PTH is followed
by processing of the pre-mRNA
through removal of intervening
sequences.
• The mature mRNA leaves the nucleus
and attaches to polyribosomes in the
cytoplasm. The signal or pre-sequence
of the hormone then binds to a signal
recognition particle that interacts with a
docking protein on the membrane of the
endoplasmic reticulum, facilitating entry
of the nascent peptide into the cisternae.
The signal sequence is removed, leaving
the precursor proPTH.
The NH2-terminal hexapeptide of this
molecule is then removed in the Golgi
apparatus, and the mature hormone,
PTH 1–84, is packaged into secretory
granules4/5/2018 9Parathyroid Hormones

9. 4/5/2018
10
Parathyroid Hormones

10. 4/5/2018
11Parathyroid Hormones

11. PTH secretion
• Secrete parathyroid
hormone
• Humoral stimuli
• Most important regulator
of Ca2+ homeostasis of
the blood
• Hypercalcemic hormone
4/5/2018 12Parathyroid Hormones

12. 4/5/2018 13Parathyroid Hormones

13. 4/5/2018 14Parathyroid Hormones

14. Difference between High (Ca2+) and low (Ca2+)
4/5/2018 15Parathyroid Hormones

15. PTH Tranasport • The two most important hormones for
maintaining calcium levels in the body
are parathyroid hormone
(PTH) and 1,25(OH)2D (the active form of
vitamin D). The major regulator is PTH,
which is part of a negative feedback loop to
maintain [Ca++]ECF (see Humoral regulation).
PTH secretion is stimulated by
hypocalcemia, and it works through three
mechanisms to increase Ca++ levels:
• PTH stimulates the release of Ca++ from
bone, in part by stimulating bone
resorption.
•
PTH decreases urinary loss of Ca++ by
stimulating Ca++ reabsorption.
•
PTH indirectly stimulates Ca++ absorption in
the small intestine by stimulating synthesis
of 1,25(OH)2D in the kidney
4/5/2018 16Parathyroid Hormones

16. Homeostasis
4/5/2018 17Parathyroid Hormones

17. Bones, Kidneys ,Intestine
• Bones : parathyroid hormone stimulates the release
of calcium from large calcium stores in the bones into
the bloodstream. This increases bone destruction and
decreases the formation of new bone.
• Kidneys :parathyroid hormone reduces loss of
calcium in urine. Parathyroid hormone also stimulates
the production of active vitamin d in the kidneys.
• Intestine:parathyroid hormone indirectly increases
calcium absorption from food in the intestine, via its
effects on vitamin D metabolism.
•
4/5/2018 18Parathyroid Hormones

18. Summary
• PTH increases blood calcium concentrations
when calcium ion levels fall below normal.
First, PTH enhances reabsorption of calcium
by the kidneys; it then stimulates osteoclast
activity and inhibits osteoblast activity. Finally,
PTH stimulates synthesis and secretion of
calcitriol by the kidneys, which enhances Ca2+
absorption by the digestive system.
4/5/2018 19Parathyroid Hormones

19. Diseases and Disorders of the
Parathyroid
• When the parathyroid releases too much
or too little PTH, it adversely affects your
body in a variety of ways. Below are
common diseases and disorders
associated with the parathyroid glands
4/5/2018 20Parathyroid Hormones

20. Hyperparathyroidism
Hyperparathyroidism:
CAUSES:
The most common disease of
parathyroid glands is
hyperparathyroidism, which is
characterized by excess PTH
hormone, regardless of calcium
levels. In other words, the parathyroid
glands continue to make large
amounts of PTH .
SYMPTOMS:
Bone pain , Muscle weekness, Long
bone fractures ,kidneystone
Treatment :
Optimize the levels of serum
calcium and phosphate ions
control of PTH and vitamin D
4/5/2018 21Parathyroid Hormones

21. Hypoparathyroidism
CAUSES
Hypoparathyroidism is the combination of
symptoms due to inadequate parathyroid
hormone production. This leads to decreased
blood levels of calcium (hypocalcemia) and
increased levels of blood phosphorus
(hyperphosphatemia).
SYMPTOMS:
Drcreased ca ions levels in blood,
sensitive nerves ,
uncontrollable spasms of the limbs
Treatment :
daily calcium and vitamin D
supplements
4/5/2018 22Parathyroid Hormones

22. Osteoporosis
CAUSES:
Osteoporosis: When one
of the parathyroid glands is
overactive, it releases too much
PTH hormone. This causes your
bones to release calcium constantly
into the blood stream. Without
enough calcium in your bones,
they lose their density and
hardness.
SYMPTOMS:
Bone pain or tenderness
neck or lower back pain due to
fractures , stoped posture
Treatment :
biphosphonates ,vitamin D
4/5/2018 23Parathyroid Hormones

23. REFERENCE
Books:
 Harpers lllustrated Biochemistry-Robert .k.Murry , Daryl.k.Granner
JOURNALS :
 The mechanism of parathyroid hormone action on calcium reabsorption by the distal tubule.
Bouhtilauy ,lajeunesse.- Endocrine society ( PUBMED) NCBI
 The Regulation of Parathyroid Hormone Secretion and Synthesis
Published in final edited form as: J Am Soc Nephrol. 2011 February ; 22(2): 216–224.
doi:10.1681/ASN.2010020186.
 parathyroid interaction: implications in chronic kidney disease-kidney international journal
Volume77, issue 4, febuary 2010 , pages 292-298
 Biosynthesis of Parathyroid Hormone
The New England journal of Medicine journal
September 14, 1978 ,DOI : 1110.1056 /NEJM 19780914299110
 The Regulation of Parathyroid Hormone Secretion and Synthesis
Journal of the American ociety of nephrology
Published online before printDecember 16, 2010, doi:10.1681/ASN.2010020186
 Stimulation of ovine placental transport of calcium and magnesium by mid‐molecule fragments of human parathyroid
hormone‐related protein
The physiological society- AD.Care , SK.Abbas , afirst published : 1 july 1990 https://doi.org/10.1113/expphysiol.1990
INTERNET
 https://en.wikipedia.org/wiki/Parathyroid_hormone
 http://emedicine.medscape.com/article/2089334-overview
 http://www.parathyroid.com/hypoparathyroidism.htm
 http://www.parathyroid.com/parathyroid-function.htm
 https://www.endocrineweb.com/conditions/parathyroid/parathyroid-function
 https://www.hormone.org/hormones-and-health/hormones/parathyroid-hormone
4/5/2018 24Parathyroid Hormones

24. 4/5/2018 Parathyroid Hormones 25