Jackson Lectures 2

Question 1

Secretion of thyroid hormones is stimulated by TSH (thyroid stimulating hormone) which is released from the anterior pituitary in response to

Answer 1

TRH (thyrotropin releasing hormone) from the hypothalamus.

Question 2

TSH receptors are on the

Answer 2

follicle cells;

Question 3

TSH also acts to increase the

Answer 3

synthetic activity of the follicle cells and stimulates hyperplasia (and replication). Stimulation of endocytosis of colloid back into follicle cell.

Question 4

80% of the T4 that is secreted is converted into

Answer 4

T3 in the liver and kidney. The extra iodide can be returned to the colloid.

Question 5

This pattern of secreting mostly T4 and then converting it into T3 once the hormone is in the circulation maximizes the

Answer 5

concentration gradient for free iodide between the blood (high) and colloid (low), and helps insure that iodide is available for thyroid hormone (TH) synthesis.

Question 6

Receptors for TH are in the nuclei of most cells of the body, and there are four

Answer 6

different receptor types. The α and β forms are encoded by 2 different genes; types 1 and 2 result from alternative splicing of the transcript. Expression of the receptor isoforms differs with respect to stage of development and target tissue.

Question 7

Receptors occupied by TH will dimerize and form a

Answer 7

DNA binding protein that regulates gene transcription. Can form homodimers or a heterodimer with retinoid-receptor.

Question 8

Unbound TH receptor often inhibits .

Answer 8

transcription

Question 9

TH regulates the synthesis of many of the

Answer 9

proteins/enzymes responsible for its effects on cellular metabolism. Unbound receptor dimers can also bind DNA and typically inhibit transcription. Making many enzymes

Question 10

TH increase

Answer 10

Na+ / K+ -ATPase activity- this can represent 15-40% of cell’s total ATP.

Question 11

TH increase synthesis of

Answer 11

respiratory enzymes

Question 12

TH increase substrate availability-

Answer 12

need more glycogen, stimulating glycogenolysis and lipolysis. Also acts in gut to absorb these nutrients.

Question 13

TH increase cellular

Answer 13

heat production

Question 14

TH effects on mitochondria-

Answer 14

stimulate increase in number of mitochondria (fission) and increase in size of mitochondria

Question 15

TH upregulation of

Answer 15

β-adrenergic receptors that are critical for responses to activation of the sympathetic nervous system; increases sensitivities to catecholamines in both the endocrine and nervous systems (vasoconstriction and contraction of cardiac muscle; critical for sympathetic stimulation), also acts on the lungs and smooth muscle

Question 16

TH regulates production of

Answer 16

growth hormone (GH)- synthesis and interacts with effects of GH in bone; formation of skeletal bone

Question 17

TH serves as a factor that regulates

Answer 17

neuronal growth; on the left there is small growth of neuron, on the right, there was excellent growth of neurons in presence on thyroid hormone; potent factor in maintenance of neural processes

Question 18

Thyroid disease one of the most

Answer 18

common endocrine: most conditions are due to hypothyroidism, more women than men.

Question 19

Most common endocrine disease is

Answer 19

diabetes in U.S.

Question 20

Hypothyroidism is most often caused by a

Answer 20

primary defect in the thyroid gland -

; 95% of cases involve an iodine deficiency or damage to the gland

Question 21

If you don’t make thyroid hormone and no negative feedback of TSH, you get

Answer 21

growth of follicular cells and number→ Goiter

Question 22

Without iodine, there is insufficient production of

Answer 22

TH → lack of negative feedback increases TRH and TSH secretion → growth of a goiter in response to TSH stimulations. Iodine deficiency can be reversed by adding iodine to the diet; iodized salt contains 1 NaI per 10,000 NaCl.

Question 23

autoimmune thyroiditis –

Answer 23

Hashimoto’s thyroiditis- antibody interferes with thyroid hormone synthesis

Question 24

damage or destruction of the gland –

Answer 24

radioactive iodine

Question 25

Secondary TH defects arise from deficits in

Answer 25

TRH or TSH synthesis and release, or receptor deficits. In other words, thyroid function is just fine, but the gland is not receiving the proper stimulatory input.

Question 26

Symptoms of hypothyroidism: • Abnormal circulating concentrations of

Answer 26

TH (low) and TSH (high)

Question 27

Symptoms of hypothyroidism: • Goiter develops if hypothyroidism is due to a

Answer 27

primary defect

Question 28

Symptoms of hypothyroidism• The symptoms of mild hypothyroidism include

Answer 28

sensitivity to cold and slight weight gain. These cases are often not diagnosed.

Question 29

Symptoms of hypothyroidism: • The symptoms of moderate hypothyroidism are due to the effects of

Answer 29

reduced β-adrenergic receptors, and the disruption of responses to catecholaminergic stimulation. These include fatigue, reduced bloodflow, changes in skin tone, sluggish gastrointestinal motilitiy and mental function.

Question 30

Symptoms of hypothyroidism: • Myxedema is a condition associated with

Answer 30

severe hypothyroidism. Severe bloating is due to accumulation of glycosaminoglycans in the extracellular / interstitial fluid; typically most obvious in the face. TH regulates enzymes that breakdown the GAGs. It affects animals as well.

Question 31

Hyperthyroidism can be caused by

Answer 31

primary defects such as thyroid tumors that produce TH without regulation by TSH, or inflammation of the gland that leads to production of excess TH.

Question 32

Graves disease is an autoimmune disease that is a common cause of

Answer 32

hyperthyroidism. Antibodies are produced against TSH, and these antibodies are able to activate the TSH receptor so there is no feedback regulation of thyroid function.

Question 33

Grave’s Disease

• TH concentrations are high even though

Answer 33

TSH (and TRH) are low due to the feedback effects of increased TH.

Question 34

• Graves disease is more common in

Answer 34

women than in men. 7x more common in women than men. Caused by antibody against TSH, can activate TSH receptor; very close structural match to TSH. Even if TH is high, there is no negative feedback on antibody even though there is negative feedback on TSH.

Question 35

Thyrotoxicosis factitia is hyperthyroidism that results from

Answer 35

consuming excess thyroid hormone either in medication or inappropriately processed meat. Typically more transient than Graves disease.

Question 36

Secondary defects causing hyperthyroidism include

Answer 36

tumors that secrete TSH without responding to feedback control by TH.

Question 37

Symptoms of hyperthyroidism : • Abnormal circulating concentrations of

Answer 37

TH (high) and TSH (low)

Question 38

Symptoms of hyperthyroidism: • Goiter can develop in cases of Graves disease caused by

Answer 38

hyperstimulation of the TSH receptor, even though TSH levels are low!

Question 39

Symptoms of hyperthyroidism: • Metabolic and nervous system responses include

Answer 39

heat intolerance, weight loss, increased appetitie, sweating, and hypersensitivity of catecholaminergic responses due to upregulation of B-adrenergic receptors. The latter resembles a general increase in activity in the sympathetic nervous system; thyroid storm. This can be damaging to cardiovascular system.

Question 40

Hyperthyroidism: • Ocular symptoms include

Answer 40

exopthalmy, lid lag, and decreased visual acuity. Graves disease

Question 41

Treatment for hyperthyroidism includes: • Surgical removal of the

Answer 41

gland, or destruction using radioactive I. Radioactive iodine will also affect or destroy other organs that concentrate iodine, e.g. salivary glands. This treatment must be followed by replacement of TH to avoid hypothyroidism.

Question 42

Treatment for hyperthyroidism includes: • Several antithyroid drugs act to inhibit

Answer 42

iodination of TYR, block the release of TH, or ameliorate the effects of TH in peripheral tissues. Can block T3 peripherally.

Question 43

• In hypothyroid adults, symptoms include…

Answer 43

o exaggerated response to narcotics and barbiturates because there is an inadequate counteracting response from the sympathetic nervous system
o myxedema resulting in swelling of lips and tongue
o diminished cardiac and respiratory function due to lack of β-adrendergic receptors; patients are susceptible to hypothermia and hypotension.

Question 44

Hyperthyroidism - • Early eruption of teeth leads to

Answer 44

malocclusion

Question 45

Hyperthyroidism: • Hypersensitivity to

Answer 45

catecholaminergic drugs, e.g. epinephrine. A hyperthyroid person will be overly sensitive to epi, leading to overstimulation that might lead a thyroid storm; heart can fail

Question 46

Hyperthyroidism: Susceptible to

Answer 46

thyroid storm which can include tachycardia, hypertension, fever, sweating, and congestive heart failure.

Question 47

The adrenal medulla is the

Answer 47

inner portion of the gland,

Question 48

Adrenal medulla develops from

Answer 48

neural crest cells.

Question 49

Adrenal medulla: is part of the

Answer 49

sympathetic nervous system (SNS), the division of the autonomic nervous system that controls the fight or flight response. This portion of the adrenal gland secretes the catecholaminergic hormones epinephrine and norepinephrine.

Question 50

The adrenal cortex is the

Answer 50

outer portion of the gland.

Question 51

Adrenal cortex It develops from

Answer 51

mesothelial cells in the intermediate mesoderm.

Question 52

Adrenal cortex: It is not part of the

Answer 52

nervous system; in response to blood-borne signals (hormones) it secretes several types of steroid hormones.