Thyroid Gland Lecture Notes

Flashcards about the thyroid gland, thyroid hormones and their synthesis, regulation, and action.

Thyroid gland

An endocrine gland that secretes hormones directly into the bloodstream.

Two main thyroid hormones

T3 - triiodothyronine; T4 – thyroxine

Hyperthyroidism

Too much thyroid hormone.

Hypothyroidism

Too little thyroid hormone.

Goitre

Swelling of the thyroid gland

Thyroid gland anatomy

Located in the neck, butterfly-shaped, two lobes united by a narrow isthmus, brownish-red, highly vascular, thin fibrous capsule containing follicles and connective tissue.

Parafollicular cells/C cells

Minority of thyroid cells (<10%); Involved in control of serum calcium homeostasis; Secrete calcitonin; Inhibits osteoclasts from resorbing/breaking down bone resulting in decrease in calcium in the blood.

Thyroid follicular epithelial cells

Majority of thyroid cells; Line the spherical follicles and surround a follicular lumen filled with colloid (thyroid hormone store); Controlled by thyroid-stimulating hormone (TSH); Responsible for the production of T3 and T4.

Thyroid hormone structure

Tyrosine-based hormones that contain iodine.

Triiodothyronine (T3)

Contains 3 iodine atoms.

Thyroxine (T4)

Contains 4 iodine atoms.

Iodine

Essential for thyroid hormone biosynthesis

Iodide uptake

Mediated by the sodium/iodide symporter (NIS), located on the basolateral cell membrane.

Thyroglobulin (Tg)

Thyroid-specific protein; Most highly expressed protein in the thyroid gland; Large glycoprotein dimer that is secreted into the follicular lumen; Serves as a scaffold for hormone synthesis and storage.

Thyroid peroxidase (TPO)

Thyroid-specific protein; Located on apical/luminal membrane; Enzyme that catalyses; Oxidation of iodide to facilitate the iodination of Tg tyrosine residues; Coupling of the iodotyrosines to form thyroid hormone

Final steps of thyroid hormone synthesis

Iodinated Tg is stored in the follicular lumen as colloid; When thyroid hormone is required, the colloid is endocytosed from lumen into vesicles; Through fusion of these vesicles with lysosomes, Tg is digested by proteolytic enzymes to release the T3 and T4; T3 and T4 are secreted into the bloodstream via thyroid hormone transporters such as MCT8.

Control of thyroid hormone synthesis

TRH = thyrotropin releasing hormone; TSH = thyroid stimulating hormone (aka thyrotropin)

TSH receptor (TSHR)

TSHR is a G protein- coupled receptor (GPCR); Located in the basolateral membrane of thyroid cells; TSH binding causes a conformational change in the TSHR; TSHR then replaces the GDP on the G protein with a GTP thereby activating it.

Thyroid hormone binding proteins

~70% bound to Thyroxine-Binding Globulin (TBG); ~10-15% bound to Albumin; ~15-20% bound to Transthyretin (TTR); Unbound (free) hormone enters the target cells.

Circulating thyroid hormones

Majority of secreted thyroid hormone is T4; T4 is a prohormone; T3 is biologically active hormone; 20% of T3 produced each day is secreted from the thyroid; Remaining 80% is generated by conversion of T4.

Conversion of T4 to T3

T4 is converted to active T3 by enzymes called deiodinases.

Deiodinase 1 (D1)

Inner and outer ring deiodinase; Can activate and inactivate TH; Secondary activator of T3; Liver, kidney

Deiodinase 2 (D2)

Outer ring deiodinase; Main activator of T3; Main source of serum T3 and also local T3; CNS, pituitary, BAT, skeletal muscle, placenta, heart

Deiodinase 3 (D3)

Inner ring deiodinase; Inactivates T3 and T4; Secondary source of serum T3; Clearance of T3 and T4 – protective role; CNS, placenta

Role of thyroid hormones

Development, Regulation of growth, Control of basal metabolic rate

Control of development and growth

Without immediate treatment (hormone replacement), humans born without a functioning thyroid gland (congenital hypothyroidism) become severely mentally deficient.

Basal metabolic rate (BMR)

The minimum energy expenditure required for the basic functions of the body while at rest; Thyroid hormone increases BMR through oxygen consumption and heat production; Alters mitochondrial activity, the major site of oxidative processes in the cell; T3 in excess can increase BMR by 60-100%. In its absence BMR is reduced to 50%

Thyroid hormone receptors

Ligand (T3)-activated transcription factors; Bind to thyroid hormone response elements (TREs); 2 receptor genes, α & β; and 2 splice variants of each

Regulation of Thyroid Hormone

HPT axis - TSH regulation – negative feedback; Thyroid hormone transporters; Deiodinase enzymes – metabolism; Thyroid hormone receptors