Hormonale aandoeningen
FA-BA205
Werkcollege 1A
Schildklier
Boron - Medical physiology chapter 49
& werkcollege vragen
Thyroid gland
▪ Anterior neck
▪ Bowtie shape
▪ Isthmus: connecting branch between left and right lobes
Follicular cells: production thyroglobulin
▪ Production: rough ER
▪ Packing in vesicles: Golgi apparatus for transporting to colloid
Parafollicular cells; C cells
▪ Production of calcitonin
▪ Role in Ca2+ and phosphate homeostasis
Thyroid colloid: proteinaceous material to store thyroglobulin; prohormone
Thyroid hormones
▪ T3: triiodothyronine
• Far more biologically active; higher affinity for thyroid hormone receptors
• rT3 (reverse T3) not biologically active
▪ T4: tetraiodothyronine/thyroxine
→ react by binding to nuclear receptors
▪ Essential for normal development, growth and metabolism
1 - 57
,Production of thyroid hormones
1. Basolateral membrane; active transport of I- into follicular cells NIS Na+/I- symporter
- 1 I- is pumped simultaneously with 2 Na+
- Stimulated by TSH
2. Apical membrane; facilitated diffusion of I- out of follicular cells pendrin Cl-/I- exchanger
3. Exocytose of thyroglobulin (Tg) into the lumen; Tg contains tyrosyl groups
4. Oxidation of I- into I katalyst; TPO thyroid peroxidase
5. Iodination of thyroglobulin in follicular lumen stimulated by TSH
- Formation of MITs and DITs
6. Conjugation of iodinated tyrosines to form T3 and T4 linked to thyroglobulin stimulated by TSH
• TPO as katalyst
- MIT + DIT = T3
- DIT + DIT = T4
7. Endocytosis of iodinated thyroglobulin into the follicular cells from thyroid colloid stimulated by TSH
8. Proteolysis of iodinated thyroglobulin; forming T3 and T4 in the lysoendosomes stimulated by TSH
- Thyroglobulin molecules recycled
9. Secretion of T4 and T3 into the circulation stimulated by TSH
- 90% as T4
- 10 % as T3
T3 much more important than T4, but T4 concentration way higher
▪ T4 more tightly bound to plasma proteins than T3
▪ Target cells convert T4 into T3 → same concentration T3 and T4 in cytoplasm of target cells
2 - 57
,▪ TR in nucleus has higher affinity for T3 than for T4
Thyroid hormones in blood
▪ Bound to plasma proteins all made by the liver
▪ TBG: thyroid binding globulin most
▪ Albumin
▪ TTR: Transthyretin
▪ T4 0.02% free in plasma
▪ T3 0.50% free in plasma
Deiodinase: conversion of T4 into biologically active T3
▪ Type I deiodinase: liver, kidneys, skeletal muscles, thyroid
▪ Type II deiodinase: pituitary, CNS, placenta
→ T2, T1 and T0 can also be formed but are not biologically active
Mechanism of action thyroid hormones
▪ Entering target cell: diffusion through cell membrane / carrier-mediated transport
▪ Binding to TRs: thyroid hormone receptors; nuclear receptors
▪ Receptors bind to DNA response elements
3 - 57
, • RXR: retinoid X receptor
• TR: thyroid hormone receptor
Effect of thyroid hormones
Hypothalamic-pituitary-thyroid axis
▪ TRH: thyrotropin-releasing hormone
▪ TSH: thyroid-stimulating hormone
▪ Negative feedback loop
Factors inhibiting TSH release
▪ High levels of T3 and T4
4 - 57
FA-BA205
Werkcollege 1A
Schildklier
Boron - Medical physiology chapter 49
& werkcollege vragen
Thyroid gland
▪ Anterior neck
▪ Bowtie shape
▪ Isthmus: connecting branch between left and right lobes
Follicular cells: production thyroglobulin
▪ Production: rough ER
▪ Packing in vesicles: Golgi apparatus for transporting to colloid
Parafollicular cells; C cells
▪ Production of calcitonin
▪ Role in Ca2+ and phosphate homeostasis
Thyroid colloid: proteinaceous material to store thyroglobulin; prohormone
Thyroid hormones
▪ T3: triiodothyronine
• Far more biologically active; higher affinity for thyroid hormone receptors
• rT3 (reverse T3) not biologically active
▪ T4: tetraiodothyronine/thyroxine
→ react by binding to nuclear receptors
▪ Essential for normal development, growth and metabolism
1 - 57
,Production of thyroid hormones
1. Basolateral membrane; active transport of I- into follicular cells NIS Na+/I- symporter
- 1 I- is pumped simultaneously with 2 Na+
- Stimulated by TSH
2. Apical membrane; facilitated diffusion of I- out of follicular cells pendrin Cl-/I- exchanger
3. Exocytose of thyroglobulin (Tg) into the lumen; Tg contains tyrosyl groups
4. Oxidation of I- into I katalyst; TPO thyroid peroxidase
5. Iodination of thyroglobulin in follicular lumen stimulated by TSH
- Formation of MITs and DITs
6. Conjugation of iodinated tyrosines to form T3 and T4 linked to thyroglobulin stimulated by TSH
• TPO as katalyst
- MIT + DIT = T3
- DIT + DIT = T4
7. Endocytosis of iodinated thyroglobulin into the follicular cells from thyroid colloid stimulated by TSH
8. Proteolysis of iodinated thyroglobulin; forming T3 and T4 in the lysoendosomes stimulated by TSH
- Thyroglobulin molecules recycled
9. Secretion of T4 and T3 into the circulation stimulated by TSH
- 90% as T4
- 10 % as T3
T3 much more important than T4, but T4 concentration way higher
▪ T4 more tightly bound to plasma proteins than T3
▪ Target cells convert T4 into T3 → same concentration T3 and T4 in cytoplasm of target cells
2 - 57
,▪ TR in nucleus has higher affinity for T3 than for T4
Thyroid hormones in blood
▪ Bound to plasma proteins all made by the liver
▪ TBG: thyroid binding globulin most
▪ Albumin
▪ TTR: Transthyretin
▪ T4 0.02% free in plasma
▪ T3 0.50% free in plasma
Deiodinase: conversion of T4 into biologically active T3
▪ Type I deiodinase: liver, kidneys, skeletal muscles, thyroid
▪ Type II deiodinase: pituitary, CNS, placenta
→ T2, T1 and T0 can also be formed but are not biologically active
Mechanism of action thyroid hormones
▪ Entering target cell: diffusion through cell membrane / carrier-mediated transport
▪ Binding to TRs: thyroid hormone receptors; nuclear receptors
▪ Receptors bind to DNA response elements
3 - 57
, • RXR: retinoid X receptor
• TR: thyroid hormone receptor
Effect of thyroid hormones
Hypothalamic-pituitary-thyroid axis
▪ TRH: thyrotropin-releasing hormone
▪ TSH: thyroid-stimulating hormone
▪ Negative feedback loop
Factors inhibiting TSH release
▪ High levels of T3 and T4
4 - 57
