Thyroid hormones

Dr. Sovan Bagchi

Professor of Physiology

www.gmu.ac.ae COLLEGE OF PHARMACY

 Learning Objectives

 Describe the synthesis and release of thyroid hormones.

 Discuss the functions and regulations of thyroid Hormones
 Discuss hypo and hyper thyroidism
 THYROID GLAND
• ACINI,
FOLLICLES
SURROUNDED
BY CELLULAR
LAYER

• FILLED WITH
PROTEIN
SUBSTANCE –
COLLOID
THYROID HORMONES

IODINATED
DERIVATIVES
OF TYROSINE
 THYROID HORMONE
SYNTHESIS
TRAPPING OF IODINE
PUMPED INTO ACINAR CELLS AGAINST
CONCENTRATION GRADIENT

ACTIVE TRANSPORT (iodine will be moved

into the cells)
• STIMULATED BY -TSH (transport of iodine to
move into thyroid
gland)
• INHIBITED BY -PERCHLORATES
• THIOCYANATES
 THYROID HORMONE
SYNTHESIS
OXIDATION
BY PEROXIDASE ENZYME TO ‘FREE IODIDE’
IODONIUM ION (I+)

PEROXIDASE ENZYME
• INHIBITED BY -METHYL THIOURACILS
PROPYL THIOURACILS
CARBIMALZOLE (drug for
treatment of hyperthyroidism)
 THYROID HORMONE
SYNTHESIS

SYNTHESIS OF THYROGLOBULIN

THYROGLOBULIN IS PRODUCED BY
ACINAR CELLS

PUSHED INTO THE COLLOID

 THYROID HORMONE
SYNTHESIS

COUPLING

• I+ ATTACHED TO THE 3-TYROSINE

MONO – IODOTYROSINE (MIT)

• I+ ATTACHED TO THE 3,5-TYROSINE

DI – IODOTYROSINE (DIT)
 THYROID HORMONE
SYNTHESIS

COUPLING

• MIT + DIT TIT (T3) more effective. major thyroid hormones

• DIT + DIT TetraIT (T4) concentration is more also major TH

• MIT + DIT’ reverse TIT (rT3)

 THYROID HORMONE

TRANSPORT
BY CARRIER PROTEINS

CARRIER PROTEIN %
CARRIED
THYROXINE BINDING GLOBULIN 60

THYROXINE BINDING PREALBUMIN 30

ALBUMIN 10
THYROID HORMONE

TRANSPORT
TWO FORMS

BOUND - ‘TOTAL’
UNBOUND - ‘FREE’
 THYROID HORMONE

THYROXINE – T4

FORM PLASMA
CONCENTRATION
BOUND T4(‘TOTAL T4’) 8 μg / dL
UNBOUND T4 (‘FREE T4’) 2 ng / dL
 THYROID HORMONE

TRIIODOTHYRONINE – T3

FORM PLASMA
CONCENTRATION
BOUND T3(‘TOTAL T3’) 0.15 μg / dL
UNBOUND T3 (‘FREE T3’) 0.3 ng / dL
 THYROID HORMONE

‘FREE’ HORMONE

I. IS IN EQUILIBRIUM WITH ‘BOUND’ HORMONE

II. CONCENTRATION IS KEPT CONSTANT IN THE

PLASMA

III. IS THE FEEDBACK INHIBITOR OF TSH AND TRH

SECRETION
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

1. CALORIGENIC ACTION
• STIMULATES METABOLISM ( NA+/K+ TRANSPORT)
• INCREASES BMR
• INCREASES O2 CONSUMPTION

(EXCEPT IN ADULT BRAIN, TESTIS, UTERUS, LYMPH NODES,

SPLEEN & ANTERIOR PITUITARY)
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

2. GROWTH PROMOTION
• ERUPTION OF DENTITION
• GROWTH & DEVELOPMENT OF CNS
• FORMATION OF OSSIFICATION CENTRES
• GENERAL BODY GROWTH (TOGETHER WITH GH)
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

3. CHO METABOLISM
• INCREASES CHO ABSORPTION IN THE GIT
• GLYCOGENOLYSIS
• GLUCONEOGENESIS

CAUSES HYPERGLYCAEMIA – “THYROID DIABETES”

 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

4. FAT METABOLISM
• DECREASES CIRCULATING CHOLESTEROL
• DECREASES PLASMA FATTY ACIDS
• DECREASES PHOSPHOLIPID
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

5. PROTEIN METABOLISM
• INCREASES BREAKDOWN OF MUSCLE PROTIEN
• INCREASES CREATININE EXCRETION
• DECREASES PHOSPHOLIPIDS

‘THYROTOXIC MYOPATHY’
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

6. EFFECTS ON CVS
• INCREASES FORCE OF CONTRACTION
• INCREASES HEART RATE
• INCREASES SYSTOLIC BP
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

7. EFFECTS ON CNS
• DEVELOPMENT & GROWTH OF CNS
• MYELINOGENESIS & SYNAPTOGENESIS
• DEVELOPMENT OF MENTAL FUNCTIONS
• INTELLIGENCE

AFFECTS BEHAVIOUR
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

8. EFFECTS ON GIT
• INCREASES GASTRIC MOTILITY
• INCREASES GASTRIC SECRETIONS
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

9. EFFECTS ON BONE
• INCREASES CALCIFICATION
• INCREASES URINE CA++ EXCRETION
• CAUSES CALCIURIA
• CAUSES OSTEOPOROSIS
 THYROID HORMONES
T4 – FIRMLY BOUND TO TBG, SLOW, LONG-ACTING
T3 – FASTER, SHORT-ACTING

ACTIONS

10. EFFECTS ON ERYTHROPOIESIS

• MILD STIMULATION OF RBC PRODUCTION
• MAY LEAD TO MILD ANAEMIA
• DUE TO BONE MARROW METABOLISM ?
• DUE TO B12 ABSORPTION FROM INTESTINES ?
 THYROID HORMONES
REGULATION
- VE
HYPOTHALAMUS

TRH
‘FREE’
- VE
PITUITARY T4, T3

TSH

IODINE THYROID
BLOOD

T4, T3 T4-TBP
T3-TBP
 THYROID HORMONES
TSH IS KEY FACTOR IN REGULATION

T4, T3 TSH

Thyroid Gland
size

GOITRE
 Learning Resources
 Text Book: Marieb EN. Human Anatomy and Physiology,
9th Edition, Pearson International Edition; 2014. ISBN-13:
978-1-2920-2649-7. Chapter 16, pp. 659-662
 Power-point presentation in the moodle

www.gmu.ac.ae COLLEGE OF PHARMACY