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

3. TSH – the background Diagnose/ monitors the Hypothyroidism
TSH is one of the best screening test for the diagnosis of the thyroid gland disorders (like hypothyroidism) and: 1
Monitors the treatment of hypothyroidism
Thyrotropin is released in response to the signals from the Hypothalamus (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 secreted by the Thyrotropes from Ant. pituitary .
It is a glycoprotein having 2 chains ,synthesized in the RER of Thyrotrope cells with CHO moiety
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

6. TSH – the structure

7. TSH - the target organs GPCR
Target cells are the ones with TSH receptors - GPCR
TSH receptors are mainly found on the plasma membrane of Thyroid Follicular cells - the Target cells
TSH stimulates G - Protein Coupled Receptors on thyroid cells to↑ the production of Thyroid hormones (TH)

8. Synthesis of TSH
Thyrotropin is synthesized by the RER of the thyrotropes of the ant. Pit. as Prohormone
It loses signal peptidase in RER and carbohydrate is added both in RER and Golgi
Both α and β chain are interlinked which is important for the bioactivity of the TSH
TSH undergoes post translational modification for the mature hormone

9. Regulation of TSH secretion – 2 pathways TH as key player
TSH secretion is regulated essentially by the negative feed back mechanism
This is achieved by 2 methods
Direct or short loop /Pituitary - thyroid axis
Indirect or long loop / Neuro - endocrine 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 Ant. Pituitary and circulating level of Thyroid hormones
When TH level is high, it inhibits the Ant. Pit. to synthesize and release TSH that:
Lowers/brings TH level from thyroid gland to normal
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 level of T3/T4 inhibits TRH from the hypothalamus and TSH as result (as well as Hypothalamic Somatostatin ) and :
It also Stimulates the secretion of TIH from the hypothalamus to
Bring back TH to normal
Opposite is true when TH level is Low (↑es TRH and TSH).

13. TSH – Neuroendocrine regulation

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

15. 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 receptor over the plasma membrane of thyroid cells
Activation of G- protein leads to the separation of α subunit from other subunits to bind with α- GDP for α- GTP

16. TSH mechanism of action cont.
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 via protein Kinase A to :
execute the actions of TSH

17. TSH mechanism of action

18. TSH - Metabolic actions As tropic hormone
TSH increases the size and NO of thyroid cells by ↑ the DNA replication and its content
↑ mRNA and translation of proteins
Promotes the growth, development and nutrition of the thyroid gland and rest of the tissues

19. 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

20. Metabolic actions of TSH cont.
Oxidation of Iodide to produce elemental Iodine
Iodination of Tyrosine - Organization
Coupling of Iodotyrosines
Release of T4 and T3
↑ in the intracellular Ca++.↑ Glycolysis and NADFPH generation

21. TSH - Serum abnormalities
TSH may be secreted in excess or there may be deficiency of TSH for the body requirements
Both the conditions give rise to different clinical conditions
These conditions are usually associated with excess or deficiency of thyroid hormones - T4 and T3

22. Hypothyroidism - TSH excess and normal TH - Cold intolerance
↑ in TSH level with normal T4 is called hypothyroidism
It is characterized by reduction in:
BMR, O2 consumption and heat production
Increases the body weight, Diabetes and CVD
Produces Cold intolerance and Constipation

23. Hyperthyroidism – T4 excess with normal /↓TSH cold tolerance
It is characterized by low/ normal TSH level with high T4
It increase in BMR,O2 consumption and heat production
Reduction in body weight .
Increase in heart rate and arrhythmias
Cold tolerance and GIT disturbances

24. 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

25. 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