Download Thyroid gland

Thyroid-2
Regulation and Mechanism of Action
lecture NO : 02 MBBS
Dr Muhammad Ramzan
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
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
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
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
Regulation of TH – Both pathways
TH - regulation
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
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
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
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
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
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)
TH - Mechanism of action
Mechanism of TH
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
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
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
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
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