1. Thyroid Stimulating Hormone - TSH Lecture NO: 2ndMBBS
Dr Muhammad Ramzan

2. Thyroid Stimulating Hormone (TSH) – the definition
TSH is the formal name of a protein hormone from the anterior pituitary gland
It is also called Thyrotropin
Thyrotropin regulates the endocrine functions of the thyroid gland
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3. TSH – the background Diagnose/ monitors the Hypothyroidism
TSH is one of the best screening test for the diagnosis of the thyroid gland disorders and:
Monitors the treatment of hypothyroidism
Thyrotropin is released in response to hypothalamic hormones - TRH and TIH
It is a tropic hormone that regulates the growth, nutrition and functions of the thyroid gland

4. TSH and hypothalamus

5. TSH - the structure A Glycoprotein- 210 AA.
TSH is a glycoprotein having 2 chains with CHO moiety, produced in the RER of Thyrotropes – Ant.Pituary gland
α = 98 AA and β = 112 AA = 210 AA. α - chain is common to all Glycoproteins – FSH and LH
β chain determines the Receptor Specificity
Separation of both the chains makes TSH as inactive
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6. Structure of TSH

7. TSH - the target organs GPCR
Target cells are the ones with TSH receptors – GPCR
The major target organ is the thyroid gland
TSH receptors are located on the plasma membrane of the thyroid follicular cells

8. Biosynthesis of TSH
Thyrotropin is synthesized as Prohormone in the RER of the Thyrotropes of Ant. Pituitary Gland
It loses signal sequence via peptidase in RER and CHO is added both in RER and Golgi apparatus
Both α and β chain are interlinked and is important for the bioactivity of the TSH
TSH undergoes post translational modification for the mature hormone

9. Regulation of TSH synthesis – 2 pathways
TSH secretion is regulated essentially by the negative feed back mechanism
This is achieved by 2 pathways
Neuro endocrine/long loop/indirect regulation
Pituitary – thyroid axis/ direct/short loop regulation
The major player is the circulating level of TH

10. Regulation of TSH – Direct pathway Pituitary - thyroid axis
It is the interaction B/W TSH from Pituitary and circulating level of TH
When TH level is high, it interacts with the TSH from the anterior pituitary and reduces TSH secretion
Opposite is true when TH level is low

11. TSH – Direct Regulation Pituitary- thyroid axis

12. TSH - Neuroendocine /Indirect/ long loop regulation
Hypothalamic - Pituitary- thyroid axis
It is the interaction B/W the circulating level of TH and Hypothalamus – TRH and TIH
High serum level of T3 and T4 inhibits TRH from the hypothalamus and TSH as result and
Stimulates the secretion of TIH from the hypothalamus 2
Opposite is true when TH level is Low (↑es TRH +TSH).

13. TSH – Neuro - endocrine regulation/Indirect Long loop – inhibition/stimulation

14. Mechanism of action of TSH -- GPCR GPCR binding with β- subunit of TSH
Mechanism of action of TSH is similar to the rest of the protein/peptide hormones
β - subunit of the TSH binds to the receptors over the plasma membrane of thyroid cells – GPCR
Activation of G - protein leads to the separation of α subunit to bind with α- GDP for α- GTP

15. TSH mechanism of action – G- protein activation
Membranous Adenylate Cyclase is activated by binding of α- GTP to the enzyme which produces:
cAMP from ATP - the 2nd messenger
cAMP causes Phosphorylation of intracellular protein/ enzymes to executes the actions of TSH

16. TSH – mechanism of action

17. TSH - Actions on thyroid cells As tropic hormone
TSH increases the size and NO: of the thyroid cell by increasing the cellular DNA content
↑ mRNA and translation of proteins
Promotes the growth /nutrition of thyroid gland

18. Metabolic actions of TSH Centered at Thyroid gland
All the endocrine functions of thyroid are carried out by the Thyroid Stimulating Hormone - TSH
These include:
Thyroglobulin synthesis
Iodine trapping

19. Metabolic actions of TSH cont.
Oxidation of Iodide for elemental Iodine
Iodination of Tyrosine
Coupling of Iodotyrosines
Release of T4 and T3
↑ in the intracellular Ca++.↑ Glycolysis and NADFPH generation

20. TSH - Serum abnormalities
The circulating level of TSH may be ↑or ↓giving rise to :
important clinical conditions
These conditions are usually associated with excess or reduction in TH levels - T4 and T3

21. TSH excess and normal TH - Hypothyroidism Cold intolerance
High TSH level with normal T4 is hypothyroidism
It is characterized by reduction in:
BMR, O2 consumption and heat production -
Increase in body weight, Diabetes and CVD and:
Cold intolerance and Constipation

22. Hyperthyroidism - Low TSH and high T4 cold tolerance
It is low/ normal TSH level with high T4
It is characterized by increase in : BMR,O2 consumption and heat production
Reduction in body weight .
↑in heart rate and arrhythmias
Cold tolerance and GIT disturbances

23. TSH – Normal serum levels
Prevalent normal serum level of TSH in adults is:
UIu/L
Recent/new TSH recommendations
uIU/L
Normal serum level of T4 for adults
11.5 to 23.5 pmol/L

24. Why TSH normal levels are reduced
NACB (National Academy of clinical Biochemistry) has suggested :
to reduce the normal range of TSH for adults to uIU/L
Adults with an initially measured TSH level of over 2uIU/L
Had an increased odds ratio of developing hypothyroidism
over (following) 20 years especially with ↑ thyroid antibodies