1. Thyroid-2 Regulation and Mechanism of Action lecture NO : 02 MBBS
Dr Muhammad Ramzan

2. Regulation of THs Regulation of TH is important to:
Control the metabolic activities of all the body cells
Promotes the body growth especially CN development in children
Provide energy to satisfy the requirements of all body reactions
Maintain BMR for essential body systems like CVS; Respiratory.GIT and maintenance of body temperature

3. Regulation of THs TH are regulated through 2 path ways:
Neuro endocrine regulation / Hypothalamus- pituitary Thyroid axis or Indirect pathway
Pituitary - Thyroid axis/direct pathway
Negative feed back is the main mechanism

4. Neuro endocrine pathway
Serum TH level is the key player in regulation of the TH
The deficiency of TH stimulates the hypothalamus to secrete Thyrotropin releasing hormone – TRH
TRH stimulates the Ant. Pituitary to secrete TSH that stimulates the thyroid gland to ↑TH (T4)
Opposite is true when serum TH level is high
Exposure to cold in children ↑ release of TRH –TSH and TH

5. Pituitary- thyroid axis/ Direct pathway TH and TSH
It is the interaction B/W TH level and Pituitary gland
Deficiency of TH causes the stimulation of Pituitary to increase the secretion of TSH
TSH stimulates and ↑ the secretion of TH from Thyroid
Opposite is true when TH is high
Hypothalamus/TRH has no role in this regulation

6. Regulation of TH – Both pathways

7. TH - regulation

8. TH – mechanism of action
TH hormones act through activation of genes similar to that of Steroids hormones
TH have nuclear receptors – Retinoid X receptors that bind with the TH to form hormone receptor complex(HRC)
HRC is translocated to the acceptor site at the nucleus Hormone Response Element HRE - the gene for TH
HRE is expressed for mRNA which translates enzymes/proteins that execute hormonal actions

9. Transport of Thyroid hormones (TH)
TH are transported in free as well in bound form with plasma proteins
Only a small fraction of TH is available in free form and is biologically active
T3 is 10 times more active than T4

10. TH - Membrane transport and cytoplasmic de iodination
Thyroxin/T4 must be de iodinated to Free T3(FT3) in the cytoplasm by Deiodinase before its :
Translocation to the nucleus
TH cross the cell membrane via the carrier mediated transporters – Iodothyronine Transporters
This is active transport and ATP dependent

11. Bound form of TH – the significance
Bound forms are attached to the Thyroxin Binding Globulin (TBG), Thyroxin Binding Pre albumen and Albumen
Bound forms are important in measuring the activity of gland

12. TH - Mechanism of Action
TH cross the cell membrane by Iodothyronine transporters to reach the acceptor site in the nucleus
Thyroxin or T4 is de Iodinated first to T3 as active TH
Bind first with the Retinoid X receptor (RXR) and then with the Hormone Response Element (HRE) at DNA
Stimulates the TH genes (HRE) to transcribe mRNA that
finds its way to the cytoplasm

13. TH - Mechanism of action cont.
mRNA translates the specific proteins/ enzymes that carry out hormone effects/actions on the :
Target cells throughout body
TH Promote the growth, metabolism and activities of other systems (CV,respiratory and body temperature)

14. TH - Mechanism of action

15. Mechanism of TH

16. General actions of TH Stimulate the genetic expression at HRE
Promote the synthesis of proteins and enzymes to promote growth, reproduction and repair
TH increases the metabolic rate of body cells, energy release and maintain the body temperature

17. Metabolic actions of TH
TH have significant metabolic actions on the :
Protein metabolism
Fat metabolism
Carbohydrate metabolism and
Maintenance of Body temperature, BMR and heat

18. Actions on Protein metabolism
Promotes genetic expression; DNA replication,DNA content, increases the no of cells for body growth and repair
TH promote protein synthesis, body growth and development of CNS especially in children
Prevents proteolysis protein
hormnes

19. Action on lipid metabolism
TH stimulates Lipid metabolism
Promotes lipolysis and ↑release of FAs from adipose tissues
Reduces adipose tissue mass/ Lipogenesis
Increases FA oxidation by ↑no of Mitochondria and activity
Plasma level of TG and CH is inversely proportional to the TH level

20. Actions on carbohydrate metabolism
Thyroid hormones stimulate Carbohydrate metabolism:
Promotes the absorption of glucose from GIT
Increases glycolysis and glucose utilization and reduces blood glucose level - hypoglycemic
Promotes Glycogenolysis
Produces hyperglycemia : Prevents Insulin secretion and promotes insulin degradation