Transcript final thy-adr

Thyroid Metabolic Hormones
Prof/Faten zakareia
Dr. Taj
Steps in the Synthesis of T3 T4
1-Iodide Trapping from plasma
2-Synthesis & secretion of Thyroglobulin (Tg) & Synthesis of
thyroid hormones occurs on Thyroglobulin within the colloid.
3-Oxidation of Iodide to Iodine.
4-Organification (Incorporation of Iodine to Tg)
5-Coupling of monoiodotyrosine & diiodotyrosine to form
triiodothyronine (T3) and t hyroxine (T4)
6-Proteolysis of Tg containing T3 and T4 by Lysosomes.
7-Release of T3 and T4 into circulation.
The functional unit of the thyroid is the thyroid follicle:
Synthesis of T3 and T4 cont….
amine hormones synthesized from the amino acid
tyrosine
I + tyrosine
MIT + I
DIT + DIT
DIT + MIT
monoiodotyrosine (MIT)
diiodotyrosine (DIT) .2
thyroxine (T4) .3
triiodothyronine (T3) .4
.1
hormones still attached to Thyroglobulin

Thyroid functions
1-Increase CHO metabolism.
2-Increase Fat metabolism. Increases mobilization and FFA
concentration& Lipolysis.
3- Increase (BMR) basal metabolic rate & increase Heat
production..
4- decrease Body weight.
5- increase Blood flow and Cardiac output & heart rate
&contraction.
6- Increase Respiration.
7- increase GIT Motility.
8- Excitatory effect on CNS& increase sympathetic effect
9- Causes both muscular weakness. (causes fine muscle tremor)
10-stimulate brain growth and maturation in fetal life & after birth
Regulation of Thyroid Hormone Release
Thyroid Dysfunctions
CRETINISM
•
Congenital absence of T3 and T4 or chronic
iodine deficiency during childhood
- retarded growth
- sluggish movements
- mental deficiencies
Adult hypothyroidism
Myxedema
Deficiency of thyroxine in adults:- low rate of metabolism and lethargy
-decreased body temp
-decreased heart rate
-outer skin becomes scaley
– swelling of sub- connective tissue &Edematous apperance
-Excessive sleep
- Muscle weakness
- Increased weight, constipation
- Decreased growth of hair
Adult hyperthyroidism
As in Grave’s Disease& toxic goiter:↑ size of the gland 2-3 times normal
↑ rate of synthesis of hormones several
folds
Symptoms:
-hyperactivity
-high rate of metabolism-high body temp
-high heart rate
- excitability,
- increased sweating
- mild to extreme weight loss,
- diarrhea
- muscular weakness
- extreme fatiuge,
- innability to sleep,
- tremors of hands.
- Exophthalmos ( protrution of eye ball)
EXAMPLES OF THYROID DISEASES
1° Hypothyroidism
Hyperthyroidism
THE ADRENAL GLANDS:
1-Adrenal cortex: secrete corticosteroid &
mineralocorticoidsd.
a2-Adrenal medulla: secretes adrenaline
-Adrenal cortex :- has three layers:
1-Zona glomerulosa (15% of the cortex) secretes
mineralocorticoids (aldosterone)
2-Zona fasciculata (75%) – secretes glucocorticoids
(mainly cortisol and corticosterone)+Androgens,
estrogens.
3-Zona reticularis – gonadocorticoids as Androgens,
+ small amounts of glucocorticoids
• Mineralocorticoids (aldosterone)
1-stimulates the Active Reabsorption of sodium
from the distal tubule into blood
• Water is passively reabsorbed with sodium which
maintains sodium concentrations at a constant
level.
• Hence extracellular fluid volume expands
2- Aldosterone facilitates Potassium Excretion (loss
from ECF ) in the urine
Functions of Glucocorticoids
1-Increases blood glucose levels by:
-(+) gluconeogenesis in the liver via stimulating the
enzymes involved in gluconeogenesis & Decreasing
utilization of glucose
2- on proteins:-Reduces protein formation (catabolic)
amino acids not transported into muscle cells , ↓
protein synthesis & ↑ amino acid blood levels
3- On fats:-Lipolytic & Mobilizes fatty acids for gluconeonesis.
↑ formation of fat in trunk areas & face but ↓ fat
(muscle) from extremities
Glucocorticoids are anti-inflammatory used to alleviate inflammation
Inhibit production of prostaglandins and leukotrines (mediate
inflammation)
They also reduce the effects of histamine
On immunity:-When administered in high doses:
Suppress antibody formation
Kill immature T and B lymphocytes
-Cortisol has mineralcorticoid effect, Not as potent as aldosterone.
BP regulation & cardiovascular function:
Sensitizes arterioles to the action of norepinephrine (Permissive
effect).
Maintains normal renal function
- Permissive regulation of fetal organ maturation
PANCREAS
A-Exocrine function:- enzymatic secretion from Acinar
cells
B-Endocrine, hormonal:The islets of Langerhans of human being contain 3 major types of
cells
1- alpha cells secrete glucagon
2- beta cells secrete insulin
3- D cells secrete Somatostatin, pancreatic polypeptide
Secreted by pancreatic β cells in response
to elevated blood glucose levels to lower
blood glucose levels.
Increases transport of glucose to muscle,
liver and adipose tissue (lowers blood
glucose levels)
Glucose enters pancreatic β cells through glucose transporter GLUT2 and
is used to produce ATP (oxidative phosphorylation)
- ATP closes ATP gated K+ channel and depolarizes the membran e of B
cells
- Depolarization opens voltage gated calcium channels
-Entry of calcium causes Exocytosis of insulin
INSULIN DEPENDENT INSULIN INDEPENDENT
All muscles. 
Adipose tissues. 
Leukocytes. 
Pituitary. 
Mammary glands. 
Lenses of the eyes. 
Brain 
Kidney tubules. 
Intestinal mucosa. 
RBCs. 
- Enhances transport of glucose into the cells & plasma
glucose levels decrease
- Activates glycogen synthase
- Activates glucokinase (storage of glucose)
- Enhances catabolism of sugar to glycerol
- Stimulates lipid synthesis
- Stimulates active transport of glucose and amino acids and
protein synthesis
-Stimulates K+ uptake by cells
- It is anabolic hormone
-Glycogenesis ↑(form glycogen)
-Glycogenolysis ↓(breakdown of glycogen)
-Gluconeogenesis ↓
Glucose transport into adipocytes ↑
Enzyme activity in adipocytes ↑ (glucose converts to
fatty acid)
FFA entry into adipocytes ↑
Lipolysis ↓
Hence it builds up fat reserves.
Amino acid (AA) Transport into muscle fibers ↑
Amino acid (AA) Incorporation into proteins ↑
Protein degradation ↓ 
It stimulates growth hormone.



Direct stimulation 
Increased plasma glucose or (AA)
levels directly stimulate β cells
Hormonal regulation 
Gastrointestinal hormones (GIP,
CCK) also stimulate β cells
Neural regulation 
Parasympathetic nervous system stimulates
β cells
Sympathetic NS inhibits β cells 

Diet 
High carbohydrate diet → β cell hypertrophy →
increased insulin secretion followed by β cell
exhaustion?? or receptor down regulation
Drugs 
Sulfonylurea derivatives - close ATPsensitive K+ channels → insulin ↑↑
Diabetes Mellitus (insulin deficiency)
Reduced glucose entry into cells
Increased glucose release from liver
Extracellular plasma glucose excess, intracellular
glucose deficiency
Impaired glucose tolerance
Decreased Amino Acid entry into cells
Lipolysis↑
Hyperglycemia
Hyperosmosis → osmotic shrinking of the cells (BRAIN!)
Glycosuria → polyuria → Polydypsia
Dehydration
Fat mobilization → Abnormal Deposition of fats → Micro and Macrovascular disease Atherosclerosis
GLUCAGON
Site of release: a hormone secreted by alpha cells of
islets of pancreas.
Functions: several effects opposite to that of insulin
The 2 effects of glucagons on glucose metabolism are:
- Breakdown of liver glycogen ( glycogenolysis).
- Increased formation of glucose from fats & proteins