Thyroid Normal Physiology Flashcards
Secretion of thyroid hormones - the hypothalamic-pituitary-thyroid axis 1-4
- Hypothalamus produces TRH (thyrotropin-releasing hormone)
- TRH stimulates anterior pituitary to produce TSH (thyroid-stimulating hormone)
- TSH binds to TSH receptor on surface of thyroid epithelial cells
- G proteins activated with conversion of GTP → GDP + cAMP
Secretion of thyroid hormones - the hypothalamic-pituitary-thyroid axis 5-8
- cAMP inc production/release of T3 and T4
- T3 and T4 circulate in bound and free forms
- On release T3 and T4 bind to receptor in target cells
- Complex translocates to the nucleus
- Binds to thyroid response elements on target genes
- Stimulates transcription of these genes
- Increase BMR
- T3 and T4 complete the negative feedback loop by suppressing the production of TRH and TSH by the hypothalamus and anterior pituitary
Synthesis of thyroid hormones (4)
The thyroid gland consists of follicles lined by cuboidal epithelial cells
- Inside is the colloid (the iodinated glycoprotein thyroglobulin) which is synthesised by the follicular cells
- Each follicle is surrounded by basement membrane, and between them are parafollicular cells containing calcitonin-secreting C-cells
Thyroid gland requires iodine from environment to synthesise hormones
Synthesis of thyroid hormones 1-5
- Thyroglobulin synthesis in follicular cells
- Uptake and concentration of iodide by the follicular cells
- Oxidation of iodide to iodine by the follicular cells which border the colloid
- Iodine moves into the colloid and attaches to tyrosine residues on thyroglobulin to form DIT and MIT, which couple together to form T3 and T4
- Secretion of T3 and T4 occurs when colloid is enveloped by microvilli on cell surface to form colloid vesicles which fuse with lysosomes; enzymes break down the lysosomes releasing thyroid hormone
Synthesis and Storage of T3 and T4 (1-4)
- Iodine taken up by follicle cells
- Iodine attached to tyrosine residues on thyroglobulin to form (MIT) & (DIT)
(Pharmacology note Inhibited by CARBIMAZOLE & PROPYLTHIOURACIL used to treat hyperthyroidism) - Coupling of MIT +DIT (T3) & 2 DITs (T4)
- Stored in colloid thyroglobulin till required
Thyroid hormones- T3
- T3 (triodothyronine) - accounts for ~10% of thyroid hormones secreted
- bound less tightly - more easily taken up
- ~4x more potent than T4
- Acts at the cellular level - major biologically active thyroid hormone
- more potent than T4
Thyroid hormones- T4 (2)
- T4 (thyroxine) - accounts for ~90% of thyroid hormones secreted
- Prohormone - converted to T3 by liver and kidney to become biologically active
Transport of thyroid hormones (7)
- In plasma, more than 99% of all T4 and T3 is bound to hormone-binding proteins
- Thyroxine binding globulin (70%)
- Thyroxine binding pre-albumin (20%)
- Albumin (5%)
- T3 is not bound very strongly to serum proteins compaired to T4 so has a more rapid onset and offset of actions
- Only unbound hormones will enter cells (<1%)
Metabolic state correlates more closely with the free than with the total concentration of thyroid hormones in the plasma
Alterations in TBG (Thyroxine-Binding Globulin) levels
Many drugs and other factors affect TBG; all may result in confusing total T4 levels so most labs will measure free T4 levels
increase TBG (4)
pregnancy
OCP
chronic active hepatitis
biliary cirrhosis
decrease TBG (4)
androgens
Cushing’s
severe systemic illness
chronic liver disease
Effects of thyroid hormone (T3)
Target virtually every tissue and throughout life to alter gene transcription and protein synthesis
Effects on target cells (10)
All cells, especially neurones
- Increase metabolic rate glucose uptake
liver tissue
- Increased glycogenolysis and gluconeogenesis
- Decreased glycogenesis
adipose connective tissue
- Increased lipolysis
- Decreased lipogenesis
Lungs
- Increased breathing rate + increased O2 demand
Heart
- Increased HR + forced of contraction+ increased O2 demand
Metabolic rate and thermogenesis (5)
- Thyroid hormones increase basal metabolic rate
- Increase number + size of mitochondria
- increased oxygen use and rates of ATP hydrolysis
- Increase synthesis of respiratory chain enzymes
- Thyroid hormones increase thermogenesis
Additional metabolic effects (8)
Carbohydrate metabolis
- Increased blood glucose due to stim of glycogenolysis + gluconeogenesis
- Increased insulin-dependent glucose uptake into cells
- Lipid metabolism
- Mobilised fats from adipose tissues
- Increased fatty acid oxidation in tissues
- Protein metabolism
- Increased protein synthesis
