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1 | P a g e
15
Rahaf AL-Jafari
Marah Qaddourah
Rahmeh Abdullah
Saleem
2 | P a g e
If you are following with the record you may notice a little bit difference in information sequences.
Hormones that function on growth
• Multiple hormones, including growth hormone (GH), insulin-like growth factors
(IGF-I and IGF-II), insulin, thyroid hormones, Glucocorticoids, androgens &
estrogens contribute to the growth process in humans.
• Among these, GH & IGF-I have been implicated as the major determinants of
growth in normal post uterine life.
• However, deficiencies (or excesses) of each of the other hormones can seriously
affect the normal growth of the musculoskeletal system as well as the growth and
maturation of other tissues.
Thyroid hormones
• We can say Thyroid hormone -as singular-; because the only hormone that
functions is T3.
- T3 is the most active
- T4 pro-hormone is almost inactive
- Reverse T3 totally inactive
• Thyroid hormones are essential in normal amounts for growth; excess does
not produce overgrowth as with GH, but causes increase catabolism of
proteins & other nutrients.
Some thyroid patients have overgrowth but it is treated like diabetes.
• Thyroxine at normal concentrations has permissive effect on the action of
GH on protein synthesis; in its absence amino acids uptake, and protein
synthesis are not much stimulated.
Similar of thyroxine and adrenaline on lipid
3 | P a g e
Note: Thyroxine means all thyroid hormones (T3 and T4)
• Reduced thyroid activity in childhood produces dwarfs who are mentally
retarded, whereas reduced GH in childhood produces dwarfs with normal
intelligence (usually).
Hypothyroidism
Childs deficiency of Thyroid
• Thyroid hormones are essential even during fetal life; for normal development
of skeleton and nervous system.
• Deficiency in Thyroid hormones produces Dwarfs called Cretins (Cretinism).
4 | P a g e
• Cretins have failure in growth and development of:
- Skeletal -Sexual -Mental
Adults deficiency of Thyroid
• Deficiency in Thyroid hormones called Myxoedema.
• Slowing up of all bodily processes (From Tissue oxidation to voice).
-Thought -Heart -skin -Respiratory -Gut movement
-Appetite -Blood cholesterol - Body temperature etc.…
• The ones who has deficiency in Thyroid hormones (Thyroxine) cannot think.
Hyperthyroidism
Note: Remember the function of thyroid hormone is to maintain basal metabolic rate.
5 | P a g e
• In this case the symptoms are:
- Dyspnea (shortness of breathing)
- Tremor
- Muscle weakness
- Graves’ Disease that results from:
1. Increase in Thyroid-stimulating immunoglobulin protein.
2. Thyroid neoplasm
3. Excess TSH secretion
4. Exogenous T3, T4
- Exophthalmos (protrusion of the eyeball) )جحوظ(:
Because of the increase in Thyroid-stimulating immunoglobulin protein TSI
Note: Thyroid-stimulating immunoglobulin causes protrusion of the eye ball,
But not in all hyperthyroidism (not in all conditions).
- Goiter (enlargement of thyroid gland) )تضخم الغدة الدرقية(
Types of Goiter:
1. T3, T4 are low (Benign non-toxic goiter) (hypothyroidism)
2. T3, T4 increase (malignant toxic goiter) (hyperthyroidism)
Note: *Goiter doesn’t only happen from increasing in T3, T4.
6 | P a g e
By making some tests not by appearance; we can
decide whether goiter is toxic or not.
Parathyroids
• Normally parathyroids 4 glands, located behind the thyroid.
• Up normally more than 4, not necessarily located behind thyroid; somewhere
else in the body.
• PTH functions on bones, kidneys and intestine (Gut) generally.
• PTH secreted by the 4 glands almost.
7 | P a g e
• There are 2 types of cells to
understand:
- Chief cells: Produce
parathyroid hormone (PTH)
- Oxyphil cells: Don’t
produce PTH, they may be
modified or depleted chief
cells that no longer secrete
PTH. (play role in
metabolism of other cells)
• Refer to what is written, why
almost?
The doctor didn’t answer 😊
• What do you conclude from this figure?
That PTH produces cAMP and two other
second messengers. PTH to function also
needs Ca+2.
The 2 second messengers:
*Diacylglycerol (DAG) for the activation
of enzymes.
* Inositol triphosphate (IP3) to increase
the calcium.
• What is PTH-r? parathyroid hormone relating protein (protein functions in
similarity of PTH=> that means it produces cAMP and 2 other second
messengers).
• Both PTH-r and PTH bind to the same receptor.
• We conclude that PTH is a protein hormone; from the second messengers.
• PTH has second messengers that means it cannot penetrate cell membrane.
PTH-r
8 | P a g e
General Information about PTH:
1. The parathyroid glands develop at 5-14 weeks of gestation.
2. PTH is a single chain protein (9600 molecular weight) that contains 84
amino acids. The biologic activity of the hormone resides within the
first 34 amino acids.
Note: *If we cut PTH and the first 34 amino acids remain, still PTH
functions. 💃
*Remember when we said about thyroglobulin (70-140 a.a) but
the activity resides in the first 70.
3. PTH interacts with receptors on the surface of the target cells
increasing the formation of cAMP, IP & diacylglycerol.
4. PTH is free in plasma with half-life 25m.
5. PTH is essential for life (because it provides calcium, without calcium
we cannot survive), without it Ca+2 falls in plasma, while
neuromuscular excitability increase, tetany & death occurs (when
tetany is severe).
Note: *Complete tetanus = continuous complete depolarization.
*Death comes at respiratory stage (system). But why not heart?
=>Heart doesn’t respond to another action potential until the
first one ends.
* A.P occupies the whole mechanical response.
6. The dominant regulator of PTH secretion is the plasma Ca+2 level.
7. Ca++ also regulates the size & the number of parathyroid cells.
8. Hypomagnesemia stimulates PTH secretion such as Ca++ but less
potent.
9. Arise in plasma phosphate concentration indirectly causes a transient
increase in PTH secretion.
10. 1,25 (OH)2 -D directly reduces PTH secretion.
9 | P a g e
• PTH functions on:
- Bones: increase bone resorption to release calcium, not from the structure
of the bones but from synovial fluid around the bone.
- Kidneys:
1- Produces Vitamin D; Vitamin D functions on Intestines to increase
calcium absorption.
While from the kidneys directly;
2- Increase calcium reabsorption.
3- Decrease phosphate reabsorption.
• Continuously at the end plasma calcium level is normalized.
• What is the normal plasma calcium level? 11mg/100ml plasma.
• When plasma calcium level reach 5-6 tetany occurs.
10 | P a g e
Hypoparathyroidism
• Calcium level is low, what happened?
Ans: Reduced mobilization of calcium and phosphate, reduced reabsorption
of calcium, deficiency of dietary calcium.
• The result of falling in the concentration of ionized calcium (conc. of calcium
falls below 6mg/dL plasma)?
Ans: Rise in plasma phosphate.
• Why tetany occurs?
Ans: the reason is Hypocalcemia; Deficiency in calcium because Na is
always entering the cells (continuous depolarization), therefore continuous
tetanus happens.
Note: calcium regulates the entry of sodium into cells.
11 | P a g e
The doctor gave us this paper
and said nothing about it. 🤷♀️
Its talking about tetany. 🌝
Hyperparathyroidism
• PTH produces calcium from the structure of the bones; Therefore, disease
occurs (Osteitis Fibrosa Cystica).
Note: Osteitis Fibrosa Cystica = softening of the bones.
The conclusion:
Hypoparathyroidism OR hypocalcemia produces tetany.
Hyperparathyroidism produces softening of the bones.
12 | P a g e
The second hormone that plays a role in calcium level: (the first one was PTH).
Vitamin D
• Vitamin D, is a major regulator of calcium & phosphate metabolism (as PTH).
• Why it is called Hormone and Vitamin at the same time?
Ans: Hormone (produced in the body, released to the blood).
Vitamin (we take it from the food).
And need both of them for normal functions in the body.
*يعني عنا نوعين لفيتامين د، واحد من الجسم وواحد من االكل.
• Vitamin D is a hormone in the sense that it is synthesized in the body,
although not by an endocrine gland; after further processing, it is transported
via the circulation to act on target cells.
• It is a vitamin in the sense that when it cannot be synthesized in sufficient
quantities, it must be ingested in minimal amounts for health to be maintained.
• Deficiency of vitamin D causes failure of bone mineralization & results in the
classic disease of rickets )الكساح( in children & softening of the bones
(Osteomalacia) in adults. +()معلومة حكاها انه شلل االطفال فايروسي
• The sterol structure of the synthesized form of vitamin D (D3) differs slightly
from the form usually ingested (D2), (Almost the same structure).
• Vitamins D3 & D2 are essentially prohormones that undergo identical processing
that converts them to molecules with identical qualitative & quantitative actions.
• Once vitamin D enters the circulation from the skin or the gut, it is concentrated in
the liver. There it is hydroxylated to 25-OH-D. this molecule is transported to the
kidney where it undergoes alternative fates (processing occurs).
13 | P a g e
• D3 from the Skin
• D2 from the food
• D2 = Ergocalciferol
• D3 = cholecalciferol
As we said, 25 derivatives
produced from both (skin +
food) then they
concentrated in the liver
then transferred into
kidneys.
• If there is need
[1,25-OH2-D]
prohormone functions.
• If there is less need
[24,25-OH2-D]
prohormone functions.
• [1,25-OH2-D], [24,25-OH2-D] and [25-OH-D] function in the body but in varying
degrees.
• 24,25-(OH)2-D is only 1/20th as potent as 1,25-(OH)2-D & mainly serves to
dispose of excess vitamin D.
• Vitamin D, 25-OH-D & 1,25-(OH)2-D circulate in plasma bound to a protein
carrier. 1,25-(OH)2-D has by far the lowest concentration & the shortest half-life
of the three.
• The activity orientation=> [1,25-OH2-D] then [24,25-OH2-D] then [25-OH-D].
• Vitamin D structure is steroid.
🏄♀️You can’t stop the waves, but you can learn to surf 🏄
Good luck
D2 D3