Download Thyroid gland

Thyroid-1- TH synthesis
lecture NO : 2nd MBBS
Dr Muhammad Ramzan
Thyroid Gland – the background
• Thyroid gland is an endocrine gland, situated at the root
of the neck on either side of the trachea
• It has got 2 lobes, connected in the middle by an isthmus
• Thyroid derives its name from Greek word for Shield for
its resemblance with Thyroid cartilage
• It is also called Adams˝ Apple for laryngeal prominence
Thyroid gland – the background cont.
• It is the largest endocrine gland and highly vascular
• Its size and weight is variable in normal physiological
conditions
• Thyroid gland commonly weighs 20-40G
Thyroid gland – Sex differences
• Thyroid is larger in females than males
• Structure and function of thyroid gland is variable in
sexual cycle, pregnancy and lactation
• Diseases of thyroid gland are more common in females
Thyroid Gland
Thyroid Gland – the secretions
• Thyroid functions in fetus (>11wks) and achieves its
maximum activity at puberty
• Thyroid gland secrets 3 hormones (TH) :
• T3 and T4 from Follicular
• and Calcitonin from Para follicular cells
Thyroid Gland – Histology
Follicular/Principal
• Thyroid gland is composed of closed follicles and are
lined with cuboidal epithelium/follicular/Principal cells
• The follicular cavity is filled with a colloid material - the
Thymoglobulin - THG
• Thymoglobulin is synthesized and secreted by the :
• Follicular cells into the cavity
TH are synthesized within THG
• Thyroid hormones (TH) are synthesized within THG
•
Each THG mole have 5-6 mol of TH - T4
• Para follicular cells are present in between the follicles
• Secreting Calcitonin, hormone
Thyroid gland Histology
Thyroid Gland- Histology
Parathyroid Glands
the chief cells
• 2 pairs of parathyroid glands are present on the posterior
surface of thyroid gland
• They secrete a hormone from their component cells the
Chief cells, Parathormone (PTH)
• PTH regulates the Calcium and Po4 ions in the
serum/ECF and activates the vitamin D
Parathyroid Glands
TH – their proportion and potency
• Thyroid gland secrets 3 hormones
• Tetra iodo thyronine, T4 or Thyroxin
1
• Triiodo Thyronine,
2
T3
• Calcitonin / Thyrocalcitonin
3
• T4 constitutes the 90-93% of the total secretion
• T3 about 7-10 %
•
Potency of T3 is 10 times more than T4
TH – the properties
free and bound forms
• TH are hydrophilic and occur in free and bound form
• Free TH are – FT4 and FT3
• Bound forms are transported with plasma proteins like
Albumin and Globulin
• T4 have more affinity for binding with proteins and have
delayed action >2 weeks thanT3
• T3 acts more rapidly than T4 and is active biologically
• T4 is converted first to T3 – Deiodination
Synthesis of TH – the essentials
• Amino acid Tyrosine and Iodine are the 2 essentials for
the synthesis of TH
• Both are available in diet and are absorbed from GIT
• 1mg of iodide/week is required for normal synthesis of
thyroid hormones (50mg/year)
Synthesis of thyroid hormones – 5 Stages
• Thyroglobulin (THG) synthesis
• Iodide trapping or iodide pump
• Oxidation of Iodide
• Iodination of tyrosine
• Coupling Reactions
Thyroglobulin synthesis (THG)
•
THG Is a large Glycoprotein, have115 -140 moles of
AA.Tyrosine depending upon the type of THG
•
It is synthesized by the endoplasmic reticulum (ER) of
the Follicular cells under the influence of TSH
•
THG synthesis is continuous and is stored as colloid in
the cavity of Follicles
Thyroglobulin synthesis
Iodide pump (Iodide Trapping)
• Iodides ingested orally, are absorbed from GIT into blood
in the same manner as chlorides
• About 1/5th of the Iodides in the blood is actively
removed by the follicular cells
•
This is achieved against a concentration gradient and is
called Iodide trapping
• The Iodine pump concentrates the iodide to about 30 –
250 times its concentration In blood when gland is active
Factors affecting Iodine trapping
• Iodine trapping is influenced by many factors
• Most important is TSH level in the blood
• Iodine trapping is ↑ with the ↑ in the serum TSH level
• I2 is also recycled through the de iodination of the
TH(10%) in liver and kidneys
Oxidation of the Iodide ion to elemental I2
• Iodide must be converted to elemental iodine for its
binding with Tyrosine to form TH
• Oxidation occurs inside follicular cells by an enzyme
called the Thyroperoxidase (TPO)
• Iodine is also present in the Follicular cells
• Deficiency or absence of TPO reduces or stops the
hormone synthesis
Iodination of Tyrosine
• Iodination of Tyrosine takes place in Follicular cavity
• and TH remain part of the Thyroglobulin
• THG and TH remain stored in the Follicular cavity and
are sufficient for months (4 months)
• TH are released through an enzymatic process
whenever needed
Iodination of Tyrosine – Organization
occurs in follicular cavity
• Iodination is the binding of Tyrosine with I2 (organization)
• It takes place in the follicular cavity where THG is
present and :
• amounts to 1/6th of the AA Tyrosine in THG
Iodination of Tyrosine – Organization cont.
the mechanism
• I2 is released from follicular cells (Exocytosis) and binds
with Tyrosine with in the THG to:
•
Form Mono to Tetra iodo thyronine (T4)
•
This binding is catalyzed by the enzyme Thyroperoxidase
(TPO) present in the follicular cells
Iodination/organization of Tyrosine
Coupling Reactions
• The Iodo tyrosine residues get coupled with one another
through the coupling reactions
• Coupling reactions give rise to different hormones
•
1mol of DIT+1mol of MIT=Tri iodo thyronine T3
• 2 moles of DIT
= Thyroxin T4
Coupling Reactions cont.
• 1 mol of MIT+1 mol of DIT
= Reverse ,rT
• rT3 is 1% and is biologically inactive
• MIT and DIT are not released into the blood
Coupling reactions
Storage of Thyroid Hormones
• TH remain as vesicles in the THG present in colloid
• One mol of THG have 5- 6 moles of Thyroxin
•
I mol of T3 for every 10 moles of T4 in THG
• Stores of TH in THG are sufficient for 4 months
• As such, symptoms of TH deficiency occurs after this
period- 4 months
Release of TH
• TH are first cleaved from THG and then released in
circulation
• Under the influence of TSH, THG droplets are taken up
by follicular cells by a process of Pinocytosis
• Fusion of the droplets with Lysosomes results in the
hydrolysis of THG and release of T3 and T4 in blood