Professional Documents
Culture Documents
Hormones
Early Studies on the Thyroid Gland
Gross and Microscopic Anatomy of the Thyroid
Gland
Production of Thyroid Hormones
Transport and Activities of T3 and T4
Regulation of Thyroid Hormone Production and
Secretion
Actions of Thyroid Hormones
Hyper- and Hypothyroidism
Histology of the Thyroid Gland
• The thyroid gland contains numerous follicles,
composed of epithelial follicle cells and colloid.
• Also, between follicles are clear parafollicular cells,
which produce calcitonin (see coming lecture on
calcium balance).
The Thyroid Gland
Thyroid Hormones
• There are two biologically active thyroid
hormones:
- tetraiodothyronine (T4; usually called thyroxine)
- triiodothyronine (T3)
• Derived from modification of tyrosine.
Differences between T4 and T3
• The thyroid secretes about 80 microg of T4, but only
5 microg of T3 per day.
• However, T3 has a much greater biological activity
(about 10 X) than T4.
• An additional 25 microg/day of T3 is produced by
peripheral monodeiodination of T4 (stay tuned….).
thyroid
T4 T3
I-
Why is Iodine Important in Thyroid Hormone
Production?
peroxidas
I- e I+
LH FSH TSH
Action of TSH on the Thyroid
• TSH acts on follicular cells of the thyroid.
- increases iodide transport into follicular cells
- increases production and iodination of thyroglobulin
- increases endocytosis of colloid from lumen into
follicular cells
Na+ K+ I- Na+
gene
ATP
follicle colloid droplet thyroglobulin I-
cell
endocytosis
thyroglobulin thyroglobulin
iodination I+ I-
T3 T4
Mechanism of Action of TSH
• TSH binds to a plasma membrane-bound, G protein-
coupled receptor on thyroid follicle cells.
• Specifically, it activates a Gs-coupled receptor,
resulting in increased cAMP production and PKA
activation.
Adenylyl
TSH Cyclase
Gsa
ATP cyclic AMP
Follicle cell
Protein kinase
A
Regulation of TSH Release from
the Anterior Pituitary
• TSH release is influenced by hypothalamic TRH, and
by thyroid hormones themselves.
• Thyroid hormones exert negative feedback on TSH
release at the level of the anterior pituitary.
- inhibition of TSH synthesis
- decrease in pituitary receptors for TRH
hypothalamus
+ TRH
TRH receptor
-
pituitary
- T3/T4
TSH synthesis
Influence of TRH on TSH Release
• Thyrotropin-releasing hormone (TRH) is a
hypothalamic releasing factor which travels through
the pituitary portal system to act on anterior pituitary
thyrotroph cells.
• TRH acts through G protein-coupled receptors,
activating the IP3 (Ca2+) and DAG (PKC) pathways to
cause increased production and release of TSH.
IP3 calcium
G protein-coupled
receptor
TRH phospholipase C calmodulin
DAG PKC
• Thyroid hormones also inhibit TRH synthesis.
Negative Feedback Actions of Thyroid
Hormones on TSH Synthesis and Release
TRH synthesis
hypothalamus
+ TRH -
TRH receptor -
T3/T4
pituitary
-
TSH synthesis
TSH binds
Thyroid gland
follicle cell receptors
Other Factors Regulating Thyroid Hormone
Levels
• Diet: a high carbohydrate diet increases T3 levels,
resulting in increased metabolic rate (diet-induced
thermogenesis).
• Low carbohydrate diets decrease T3 levels,
resulting in decreased metabolic rate.
• Cold Stress: increases T3 levels in other animals,
but not in humans.
• Other stresses: increased or decreased?
• Any condition that increases body energy
requirements (e.g., pregnancy, prolonged cold)
stimulates hypothalamus TRH TSH (Pit)
Actions of Thyroid Hormones
• Effects on carbohydrates:
-low doses of thyroid hormone increase glycogen
synthesis (low metabolic rate; storage of
energy)
- high doses increase glycogen breakdown (high
metabolic rate; glucose production)
Mechanism of Action of T3
• Held in storage
• Bound to mitochondria, thereby increasing ATP
production
• Bound to receptors activating genes that control
energy utilization
• Exert a calorigenic effect
Thyroid Hormone Actions which
Increase Oxygen Consumption
• Increase mitochondrial size, number and key
enzymes
• Increase plasma membrane Na-K ATPase
activity
• Increase futile thermogenic energy cycles
• Decrease superoxide dismutase activity
Effects of Thyroid Hormones on
the Cardiovascular System
• Increase heart rate
• Increase force of cardiac contractions
• Increase stroke volume
• Increase Cardiac output
• Up-regulate catecholamine receptors
Effects of Thyroid Hormones on
the Respiratory System
• Increase resting respiratory rate
• Increase minute ventilation
• Increase ventilatory response to hypercapnia
and hypoxia
Effects of Thyroid Hormones on
the Renal System
• Increase blood flow
• Increase glomerular filtration rate
Effects of Thyroid Hormones on
Oxygen-Carrying Capacity