Thyroid gland Flashcards
What does hypo release which acts on pituitary
TRH
What does pituitary release which acts on THG
TSH
Thyroid glands
C cells release calcitonin which regulates Ca2+ homeostasis
THG releases thyroid hormones
Thyroid hormones
Thyroxine (T4) Tri iodothyronine (T3)
What’s required for action of THG
Dietary iodine
Thyroid hormones action
Act on nuclear receptors to regulate gene transcription (TRE’s- thyroid response element) in target genes
Effect on metabolism
protein (lipid, carbohydrates) metabolism
Leading to growth
Body weight effects
Regulated BMR
THG structure
L and R lobes
Well vascularised
Has thyroid follicles which store thyroglobulin (tyrosine residues). This is stored in the centre of follicles, and the follicle cavities are surrounded by epithelial cells , where synthesis of hormones takes place.
Core contains protein rich element: colloid
C cells adjacent to follicles
Blood vessel capillaries directly associated with follicle cells, allowing direct release of hormones into the blood
TH synthesis
Iodination of tyrosine occurs at 2 sites either to form MIT (mono-iodotyrosine) or DIT (di-iodotyrosine)
Then there is coupling of MIT and DIT to make T4/T3
Tyrosine residues bolted together to form Thyrogobulin
T4
thyroxine
DIT +DIT
T3
Triiodothyronine
DIT +MIT
What happens after formation of T3 and T4
Iodinated thyroglobulin enters lumen (colloid) by exocytosis, from epi follicle cells where it is synthesised
Stored thyroglobulin re-enters follicle cells by endocytosis
Lysosomal enzymes release T3 and T4
MOst are bound by binding proteins in plasma
‘Free’ fraction of T3 and T4 can enter target tissues
Inside the follicle cells
Tyrosine residues form thyroglobulin
Iodine taken up by iodide transporters into cells- cotransported with NA ions
Peroxidases iodinate tyrosine residues under influence of thyroid peroxidase
When you need thyroid hormone it is endocytosed back into the cell where T3 and T4 are liberated by lysosomal digestion (from thyroglobulin) and released into the blood
Remaining tyrosine residues recycled (ie make throglobulin again)
Whole process requires TSH to be released fro pituitary- lysosomal digestion occurs under influence of TSH
TRH (Hypo) under influence of
GH (-ve)
Cold (+ve)
Sympathetic activation (+ve)
Cortisol (-ve)
TSH (anterior pituitary) under influence of
TRH (+ve)
Somatostatin (-ve)
Incr TSH causes
Incr I uptake, incr T3 and T4 synthesis in thyroid gland- released into blood
T3 and T4 feedback
+ve onto Somatostatin
-ve onto TRH release and TSH
TSH
TH production requires TSH
+ iodine uptake from blood by pump
+ TH synthesis by iodinase
+ thyroglobulin breakdown by lysosomal proteases
TH’s involved in
Growth and development
Stimulate protein, carbohydrate and lipid metabolism
Regulate energy metabolism
Body temp
Regulation of nervous system, CV, musculo-skeletal and reproduction
Actions of TH’s
Most is released as T4
Most of both T3/T4 are bound by thyroid binding globulin rest by thyroid binding prealbuin
Only unbound T3 and T4 can enter target tissues
Most physiological effects of TH’s are due to T3
TH receptors
regulate gene transcription
Actions of TH’s on mitochondria
receptors incr in size and number
Incr ATP production due to binding to receptor
Nuclear receptor increases transcription and translation via TRE’s
Incr in enzyme synthesis
Effect of TH’s on BMR
BMR= amount of calories body needs at rest
Stimulates BMR to incr over days
How does TH incr BMR
TH’s enter cell, bind to TH receptors, stimulating synthesis of NA+/K+ ATPase
Leads to incr heat production, so incr BMR
Also, TH binding leads to incr size, number and SA of mitochondria- incr rate of ATP production (same affect on heat –> incr BMR)
How does TH stimulate protein metabolism
TH binding to TH receptor triggers incr protease synthesis, incr protein breakdown, more energy expenditure, so incr BMR
Also stimulates incr protein synthesis, so tissue growth
catabolic/anabolic balance as TH is dose dependent
Low TH
anabolic
High TH
catabolic
How does TH stimulate carbohydrate metabolism
T3/T4 binding to TH receptor
Leads to general incr in enzyme synthesis:
- incr release of insulin, leads to incr glycogenesis
- Incr glucose uptake by GI tract, liver and muscle
- Incr gluconeogenesis
-Incr glycogenolysis
Balance of gluconeogenesis/glycogenolysis is TH dose-dependent
How does TH stimulate fat metabolism
ADD
TH binding to receptors stimulates incr lipoprotein receptors on liver cells, so incr cholesterol secretion, and decr plasma cholesterol
Also incr lipase synthesis, so incr lipid metabolism, so incr plasma free fatty acids
Physiological effects of TH
Body weight:decreased, incr appetite
CV: incr CO, positive inotropic vasodilation, incr BV, incr pulse pressure
Respiration: incr depth, incr rate
Muscle: incr tension, incr force of contraction
CNS: incr excitability, incr speed of thought
GI tract: incr secretions, incr motility
Underactive TG
high colloid levels
incr TSH- lose negative feedback onto it
flattened cells
Storing more thyroglobuln
HIghly active TG
low colloid levels
columnar cells
Hypothyroidism
incr TSH due to incr TRH decr T4/T3 Caused by autoimmune disease, iodine deficiency, altered H-P activity Swelling of TG (not always) fatigue lose thyroid hormone negative feedback
Hypo factors
Bodyweight: incr, decr appetite
GI: constipation
CNS: sluggish mentally, fatigue, somnolence
Muscle: weakness, stiffness, swelling
Trophic effects: decr hair growth, loss of hair, scaly skin, brittle nails
CV: decr CO, decr force of contraction, decr rate “, decr BV, heart enlargement and arteriosclerosis
Other: husky voice, myxedema, decr fertility incr menstruation, cold intolerance
Hyperthyroidism
Gland incr in size and incr rate of secretion
Largely autoimmune disease- graves disease- antibodies bind to TSH receptors and continually activate them
May also be caused by thyroid adenoma secreting lots of TH
Hyperthyroidism factors
Bodyweight: decr, incr appetite, incr food intake
CV: CO, incr contraction force and rate, incr BV, vasodilation, atrial arrthymias , congestive heart failure
Trophic effects: excess hair growth, separation of fingernails, hair loss
GI tract: incr bowel movements
CNS: nervousness, irritability, emotional instability, sleeplessness
Other: fatigue, myedema, expothalmus,amennorhea, heat intolerance, sweating
T4 conversion into T3
by deiodonases (enzymes) in target cells
Major thyroid hormone
T3
thyrosine peroxidase
oxidises iodides and attaches them to tyrosines on thyroglobin
Goiter
enlarged THG
Where in the cell are receptors for TH present
nucleus
