Physiology 2130 Lecture Notes - Lecture 57: Nerve Growth Factor, Basal Metabolic Rate, Parathyroid Gland
1 May 2018
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Lecture 057: The Thyroid and Parathyroid
The Thyroid Gland
● Found in the next
● Largest endocrine gland
● Controls energy usage
○ Energy, HR, and basal metabolism rate
● Store iodine
● Produces T3, T4, Calcitonin (not well characterized in humans)
Anatomy of the Thyroid Gland
● Lots of thyroid follicles surrounding a colloid (large mass of protein)
● Thyroglobulin (Tg) is a protein in the colloid
○ 660 KD (very high molecular weight! Large!)
○ Glycosylated
○ 2 subunits
○ 330 tyrosine residues
■ Recall: thyroid hormones are main derived from amino acids (tyrosine)
■ Carrier protein of tyrosine
○ Thyroid exploits the available of the tyrosine residues in the Thyroglobulin to
produce T3 and T4
Role of Thyroid Hormones
● Early Growth and development
○ Required for GH secretion and actions
○ Essential for early neural development via induction of nerve growth factors
(NGF)
○ Lack of T3/T4 in expecting mother leads to growth retardation and cretinism in the
infant
■ This is seen in third world countries where the diet is deficient in iodine
● Increase mitochondrial growth, replication and activity
○ Thus increase basal metabolic rate activity
■ Increase heat production, O2 demand, HR, SV
● Stimulates Na+/K+ ATPase activity and β-adrenergic receptors (heart)
○ To match increased metabolic demands (increase glucose production and
energy availability)
● Increase transcription of energy metabolism enzymes
○ These enzymes will liberate energy from a higher order form to a more readily
available form
○ Thyroid hormones increases lipids breakdown (lipolysis), glycolysis,
gluconeogenesis
■ To Increase blood metabolites levels and cellular uptake
● T3 and T4 is permissive to GH action and necessary for induction of PRL, GH, surfactant
and NGF expression
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The importance of Iodine
● Humans require 60 mg of iodine a day
○ Marjory comes from salt, seafood and dark green vegetables (kelp)
● Has an important in the production of thyroid (T3/T4) hormones for growth, physical and
mental development
○ Occurs by actions of thyroid peroxidase (TPO)
● TPO make T3/T4 via iodinated and coupling of tyrosine residues
○ Occurs in Thyroglobulin at the apical microvilli surface of the follicular cell
○ Can iodinate them once (monoiodotyrosine) or twice (diiodotyrosine)
○ Couple one monoiodotyrosine and one diiodotyrosine to get triiodothyronine
(T3) or two diiodotyrosine to make thyroxine (T4)
The Iodine Trap
● On the basolateral side, sodium/iodide symporter will use the Na+ gradient to transport I-
into the thyroid cell
● Pendrin transports I- into the lumen (facing the colloid/Tg/tyrosine residues) for oxidative
coupling to thyroglobulin
○ Allows for the production of T3/T4
● The T3/T4-thyroglobulin complex is brought back within the follicular cell via pinocytosis
○ Intracellular enzymes then liberate T3/T4 from thyroglobulin
● T3/T4 can now pass through the basolateral membrane to get the the bloodstream to
target distant receptors
TSH binding to it receptor stimulate multiple activity in the thyroid cell
● Increase activity of NIS
○ More iodine is brought into the cell
● Increase Tg production
○ More tyrosine residues
● Increase TPO activity
○ Increase production of T3 and T4
Thyroid Hormone Transport
● Thyroid hormones are aromatic
○ Insoluble in water
○ Requires carrier proteins
● Thyroxine Binding Globulin (TBG)
○ High affinity
○ Major transporter (binds 75% of circulating T3 and T4)
● Transthyretin (TTR)
○ Lower affinity than TBG
○ Binds 5% of circulating T3 and 20% circulating of T4
● Human Serum Albumin (HSA)
○ Low affinity
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find more resources at oneclass.com
○ Binds 20% of circulating T3 and 5% circulating of T4
● Carrier proteins regulates the bioavailability and t1/3
● Without carrier proteins, thyroid hormones are rapidly cleared from circulation
○ Thus carrier proteins are important!
Serum T3 and T4 Profile
T3
T4
% of hormone secreted
10%
90%
% of free in plasma
1%
0.1%
Relative activity (potency)`
10
1
t1/3 (days)
1
7
● T3 is more potent but less stable, T4 is more stable but less active
○ Because it is more stable, serum T4 > T3
● T3 is also the ACTIVE form of thyroid hormone (since it is more potent)
○ T4 is converted to T3 by cell specific deiodinase enzymes in the cytoplasm of the
target tissue
■ D1-D4 in the liver
● D2
○ Converts T4 -> T3
○ Converts T3 -> T2 (weak thyroid hormone)
● D3
○ Converting T4 to reverse T3 (rT3) an inactive form of T3
● Amount of D2 and D3 determines the level of thyroid hormone response
○ Wants lots of D2, little D3 to get high response
● T3 binds to the thyroid receptor (TR)
○ TR is a nuclear receptors
■ Activates thyroid receptor target genes
● By removing a co-repressor and recruiting a co-activator
Hypothyroidism
● Deficiency in thyroid hormone production
● Symptoms
○ Lack of energy, slow HR, feeling cold (low basal metabolic rate)
○ Muscle cramping,
○ Puffy eyes
○ Lack of concentration and poor memory
1. Endemic Goiter
● Low iodine bioavailability leading to hyposecretion of T3 and T4
● Leads to excessive TSH secretion
○ No negative feedback
● TSH stimulating leads to thyroid cell hypertrophy
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Produces t3, t4, calcitonin (not well characterized in humans) Lots of thyroid follicles surrounding a colloid (large mass of protein) Thyroglobulin (tg) is a protein in the colloid. Recall: thyroid hormones are main derived from amino acids (tyrosine) Thyroid exploits the available of the tyrosine residues in the thyroglobulin to produce t3 and t4. Essential for early neural development via induction of nerve growth factors (ngf) Lack of t3/t4 in expecting mother leads to growth retardation and cretinism in the infant. This is seen in third world countries where the diet is deficient in iodine. Stimulates na+/k+ atpase activity and -adrenergic receptors (heart) To match increased metabolic demands (increase glucose production and energy availability) These enzymes will liberate energy from a higher order form to a more readily available form. Thyroid hormones increases lipids breakdown (lipolysis), glycolysis, gluconeogenesis. To increase blood metabolites levels and cellular uptake.
