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Endocrine 5
Thyroid and Adrenal hormones
35
Physiology
3rd Grade
11/26/2014

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Term
Where is the thyroid gland found?
Definition
on both sides of trachea, below larynx
Term
Describe the structure of the thyroid gland (3 points)
Definition
-heavily vascularised
-single layer of epithelial cells secrete thyroid hormones
-lumen filled with colloid (protein rich fluid)
-parafollicular cells secret calcitonin
Term
Describe the steps involved in the synthesis of thyroid hormones
Definition
1. Active uptake of iodine
-iodide actively transported through follicular cells
-accumulates in colloid as iodine (I2)

2. Iodination of thyroglobulin
-Tgb released into lumen
-Tyrosine peroxidase binds I2 to tyorosine residues

3. Tgb-I2 uptake
-endocytosis brings the complex from colloid into cells, where it fuses to lysosomes and is split into thyroid hormones
Term
Describe the structure and release of Thyroid Hormone
Definition
-each tyrosine residue has 2 possibly sites for I2 binding
(monoiodotyrosine vs diiodotyrosine)

T4 = 2 cleaved diiodotyrosines = Thyroxine
T3 = 1 monoiodotyrosone + 1 diiodotyrosone = Triiodothyronine

-T3 & T4 are lipophilic, can diffuse across basal membrane into interstitial space then into blood capillaries
-will then bind to carrier proteins in the blood
Term
What proportion of thyroid hormones are T3, and what proportion are T4?
Definition
T3 10%
T4 90%
Term
Describe the transport & metabolism of Thyroid Hormones
Definition
-TBG carrier protien binds majority of circulating hormones, some are free, remainder are bound to albumins
-only the free portion is active and can diffuse into tissues
-T4 is transformed into T3 into tissues cells, which is degraded after acting
Term
What happens to I2 after T3 has done its job in the target cell?
Definition
it is deiodinated, diffuses out of cell, degraded
Term
Which is the active form of TH in tissues T3 or T4? Why?
Definition
T3

the nuclear TH receptor in target cells has a much higher affinity for T3
Term
Describe the action of Thyroid Hormones in their target cells (6 points)
Definition
-T4 is converted to T3, binds to nuclear receptor, activates gene transcription

-increase basal metabolic rate of cells, increase heat production & O2 consumption
-also stimulate secretion of GH during development (important for bone & tissue growth)
-increase # of (nor)adrenalin receptors
-essential for normal function of gonads
-increase velocity of nerve conduction
Term
What happens if TH is deficient during late gestation and early after birth?
Definition
-improper brain function (cretinism)
Term
How is Thyroid Hormone regulated?
Definition
1. TRH from hypothlamus increases TSH from pituitary
2. TSH binds to receptor on follicular cells, stimulate cAMP pathway, stimulates endocytosis of Tgb-I2 & TH synthesis
3. TH creates negative feedback on pituitary & hypothalamus
Term
What happens if an animal is exposed to cold for a long period of time?
Definition
TRH release will increase, stimulating pituitary to release TSH which will in turn upregulate the release of Tgb-I2 & TH to increase metabolism and produce more heat
Term
What is primary hypothyroidism? Secondary hypothyroidism? How can you treat it?
Definition
Primary: low T4 & T3 concentrations, yet high TSH, usually due to damage to follicular cells of thyroid
Secondary: low TSH secretion, usually due to pituitary/hypothalamus damage

-use the drug thyroxine
-make sure adequate iodine in diet
Term
What is goiter?
Definition
enlarged thyroid gland

-due to iodine deficiency, tumors etc
-Low T4/T3 = no feedback, so TRS & TSH are released causing hyperplasia & hypertrophy of follicular cells of thyroid to try and increase the T3/T4 production
Term
What is hyperthyroidism? How can you treat it?
Definition
Overproduction of T3/T4

-increases metabolism, excitability/nervousness, heart rate, respiration, digestive tract activity all increase

Treatment: surgery or radioactive I2 to destroy follicular cells
Term
Describe the location & structure of the adrenal glands, and the types of hormones secreted
Definition
-cap the kidneys

-consist of outer cortex layer & inner medulla layer
-produces steroid hormones

Medulla: produces catecholamines (nor)epinephrine

3 zones of outer cortex
glomerulosa - mineralcorticoids
fasiculata - glucocorticoids
reticularis - androgens
Term
What type of nerve structure is the adrenal medulla equivalent to?
Definition
a ganglion
Term
How are the hormones of the adrenal cortex produced?
Definition
-cholesterol is converted into a variety of hormones via enzyme action
Term
What major enzyme is involved with the conversion of cholesterol to various steroid hormones?
Definition
Cytochrome-P450
Term
Describe the synthesis, secretion & circulation of mineralcorticoids
Definition
Synthesis: stimulated by angiotensin & [K+] in cortical cells

Secretion: stimulated by above, plus ACTH (minor)

Circulation: loosely bound to cortisol binding globulin (CBG)
Term
What is the most potent mineralcortioid
Definition
aldosterone
Term
Describe the action of mineralcorticoids such as aldosterone
Definition
-binds to receptor in target cell
-increases gene transcription for Na/K pumps in basolateral mmb and Na channels in apical membrane
-stimulates the reabsorption of Na & secretion of K in the distal kidney tubules & collecting ducts
Term
What is the most potent glucocorticoid
Definition
cortisol
Term
What do glucocorticoids do?
Definition
regulate glucose metabolism by entering target cells, binding to receptors & stimulating/inhibiting gene transcription
Term
Describe the permissive action of glucocorticoids
Definition
-activates transcription of enzymes that facilitate the action of other hormones
Term
Describe the effect of stress on cortisol production and what results from this
Definition
-increases cortisol production
-enhances the effect of norepinephrine on blood pressure
-stimulates gluconeogenesis & inhibits tissue use of glucose to increase blood [glucose]
-stimulates fat/protein degradation to increase levels in blood

Overall effect: inhibit growth, energy conservation during periods of stress
Term
Describe the anti-inflammatory effects of glucocorticoids
Definition
-inhibits formation of prostaglandins & cytokines
-reduces lymphocyte migration
Term
How are glucocorticoids regulated?
Definition
1. hypothalamus releases ACTH-RH
2. stimulates ant. pit. to release ACTH
3. ACTH binds to receptor on cell surface of adrenal cortex, increases cAMP
4. Cholesterol is mobilized for action by P-450
5. Glucocortoids produced
6. ACTH has negative feedback on ACTH-RH
in hypothalamus
7. Glucocorticoids have negative feedback on hypothalamus AND pituitary
Term
What is Addison's disease?
Definition
Glucocorticoid deficiency

-destruction of adrenal cortex cells = no negative feedback = excess ACTH secretion
Term
What is Cushing's disease?
Definition
Overproduction of glucocortoids (cortisol)

-often due to tumours on pituitary or adrenal cortex
Term
What are androgens similar to?
Definition
testosterone
Term
What role do androgens play in females?
Definition
transformed to estrogen in adipose tissue
-are the sole source of estrogen after menopause
Term
What controls the secretion of catecholamines from the adrenal medulla?
Definition
-Ach released from preganglionic sympathetic nerves
-Ach depolarizes medulla cells, induce Ca2+ entry & exocytosis of hormones
Term
Describe the action of catecholamines
-type receptor they bind to
-alpha receptor effects
-beta receptor effects
-effects on skeletal muscle
Definition
Bind to adrenergic receptors (alpha & beta)

Alpha cells associated with SNS
-constrict smooth muscle in arterioles & sphincter of GI tract

Beta cells associated with cardiac muscles (increase contraction) and bronchioles (inhibit contraction)

Skeletal muscle
-low epinephrine levels activate B receptors (relaxation)
-high levels activate alpha receptors (contraction)
Term
What direct & indirect effects does stress have on the body?
Definition
Direct: sympathetic system acts on innervated organs

Indirect: increase catecholamine release
-increase cortisol secretion via ACTH-RH & ACTH
-increased alertness, higher heart rate & BP, higher blood [glucose], increase thyroid hormone secretion
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