Endocrine 2

Question 1

What are the endocrine hormones?

Answer 1

Thyroxine(T4)

Triiodothyronine (T3)

The thyroid hormones play key roles in the regulation of the body development and govern the rate at which metabolism occurs in individual cells

These hormones are not essential for life but without them, cellular housekeeping moves at a slower pace, eventually influencing the ability of individual cells to carry out physiologic functions

Question 2

What are the sources of iodine?

Answer 2

• fish(such as cod and tuna), seaweed, shrimp, and other seafood, which are generally rich in iodine
• Dairy products (such as milk, yogurt, and cheese) and products made from grains (like breads and cereals)
• fruits and vegetables contain iodine, although the amount depends on the iodine in the soil where they grew and in any fertilizer that was used.
• Iodized salt (table salt). Processed foods, however, such as canned soups, almost never contain Io sized salt

Question 3

Give an overview of the thyroid

Answer 3

To maintain normal thyroid hormone secretion, 150 ug of iodine is the minimal intake necessary

• functional unit of the thyroid is the follicle
• lumen is filled with thyroglobulin which contains large number of thyroid hormone molecules
• surrounding the lumen are follicle cells, which function to both synthesize and release thyroid hormone

Question 4

Explain thyroid hormone synthesis

Answer 4

1. Iodine transport- iodine uptake is via a Na/K+-ATPase powered Na/I-symporter on the basal membrane
   - This pump can raise the concentration of I- within the cell as much as 250 times that of plasma
   - Along the apical membrane, the I- is transported into the lumen by a sodium-independent transporter called pendrin
2. Thyroglobulin synthesis- high molecular weight protein is synthesized in ribosomes, glycosylated in the endoplasmic reticulum and packaged into the vesicles in the Golgi apparatus
3. Oxidation of I- to I^o
   - The enzyme thyroperoxidase(TPO), which is located at the apical border of the follicle cell, catalyzes the oxidation

Note: TPO also catalyzes Io donation and coupling

4. Iodination- As thyroglobulin is extruded into the follicular lumen, a portion (20%) of its tyrosine residues are iodinated
   - The initial products of iodination are mono and diiodotyrosine (MIT & DIT) respectively, with the latter form predominating
5. Coupling- when two DITs couple, tetraiodothyronine (T4) is formed
   - When one DIT and one MIT combine, triiodothyronine(T3) is formed.
6. Storage of thyroid hormone- enough hormones is stored as iodinated thyroglobulin in the follicular colloid to last the body fir 2-3 months

Note: when iodine is abundant, mainly T4 is formed but when iodine becomes scarce the production of T3 is increases

Question 5

Explain stimulation of thyroid hormone release

Answer 5

Hypothalamic regulator:

Thyrotropin- releasing hormone(TRH) is released in response to thermoreceptor, metabolic signals and circulating levels of T4 and T3

• In the peripheral tissues, T4is converted to T3 by 5’-deiodinase
• Free T4 and T3 inhibit the synthesis and release of TSH by thryptrophs of the anterior pituitary

Note: because the main circulating firm is T4, it is T4 that is responsible for most of the negative feedback

Question 6

Summarize thyroid hormone release

Answer 6

Hypothalamic nuclei secrete thyrotropin-releasing hormone (TRH) into portal vessels stimulating thyrotrophs of anterior pituitary to secrete TSH

This stimulates the thyroid gland, causing thyroids to secrete T4(50) and T3(1)

Within the thyrottoph, thyroid hormones decrease the sensitivity of the thyrotroph to TRH, thereby decreasing TSH secretion

Question 7

Explain the hypothalamic pituitary thyroid axis

Answer 7

Thyrotropin releasing hormone (TRH) stimulates and somatostatin(SRIIF) inhibits thyroid-stimulating hormone(TSH) release by acting directly on the thyrotroph. The negative-feedback loops shown in blue inhibit TRH secretion and action on the thyrotroph, causing a decrease in TSH secretion. The feedback loops shown in red, stimulate somatostatin secretion, causing a decrease in TRH secretion. SRIF, somatostatin of somatotropin release-inhibiting factor

Question 8

What are the overall effects on the thyroid by TSH?

Answer 8

Rapidly induced TSH effects

TSH tends to rapidly increase (minutes to hours) all steps in the synthesis and degradation of thyroid hormone, including:

1. Iodide trapping
2. Thyroglobulin synthesis and exocytosis into the follicular lumen
3. Pinocytotic reuptake of iodinated thyroglobulin back into the thyroid follicular cell
4. Secretion of T4 into the blood

Slowly induced T4 into the blood

Changes that occur more slowly (hours to days) in response to TSH include:

1. Increased blood flow to the thyroid gland
2. Increased hypertrophy/ hyperplasia of the thyroid cells, which initially leads to increased size of the gland

Question 9

What is the physiologic action of the thyroid hoemone on metabolic rate?

Answer 9

Metabolic rate

• thyroid hormone increases metabolic rate, as evidenced by increased O2 consumption and heat production
• Increases activity of Na+/K+-ATPase in many tissue
• Thyroid hormone are necessary for brain maturation and essential for normal menstrual cycle

Note: hypothyroidism leads to menstrual irregularities and infertility

Question 10

How does thyroid hormone affect carbohydrate metabolism?

Answer 10

Increases rate of glucose absorption from the small intestine

Question 11

How does thyroid hormone affect lipid metabolism ?

Answer 11

• Accelerates cholesterol clearance from the plasma
• Required for the conversion 9f carotene to vitamin A

Note: hypothyroid individuals can suffer from night blindness and yellowing of skin

Question 12

What are the cardiovascular effects of thyroid hormone?

Answer 12

• Have positive inotropic and chronotropic effects on the heart
• Cardiac output is increased, and both heart rate and stroke volumes are elevated
• Thyroid hormone in the normal range are required for optimum cardiac performance

Question 13

What are the effects of thyroid hormone on growth and maturation ?

Answer 13

Thyroid hormones act synergistically with growth hormone and somatomedins to promote bone formation

-Without adequate thyroid hormone during the perinatal abnormalities rapidly develop in the nervous system leading to mental retardation (cretinism-a form of dwarfism with mental retardation)

Question 14

What are the additional effects of Thyroid hormone?

Answer 14

• Maintains the ventilatory response to hypoxia increase erythropoieti, increase gut motility and bone turnover
• primary hypothyroidism is associated with increased prolactin

Note: TRH in excess amounts will stimulate prolactin

Question 15

What is calcitonin?

Answer 15

Calcitonin is a peptide hormone secreted by a para follicular cells of the thyroid gland

Calcitonin lowers plasma calcium by decreasing activity of osteoclast, thus decreasing bone Reabsorption

Note: Calcitonin is not a major regulator of plasma calcium. No disease has been associated with excess or deficiency of this hormone

Question 16

How does increased calcium affect bone reabsorption ?

Answer 16

1. Increased plasma calcium leads to parafollicular cells which increase CT secretion. This leads to increased CT
2. Increased CT secretion, then increases plasma CT which decreases bone Reabsorption which then decreases calcium release. Calcium release, decreases plasma calcium
3. Increased plasma CT caused decreased phosphate Reabsorption in the kidneys, which leads to increased urinary excretion of phosphate. This results results in decreased plasma phosphate
4. increased plasma CT results in decreased calcium Reabsorption in the kidneys. This leads to increased urinary excretion of calcium which also leads to decreased plasma calcium

Question 17

What is the role of thyroid hormones for development of CNS?

Answer 17

• Inhibit nerve cell replication
• Stimulate growth of nerve cell bodies
• Stimulate branching of dendrites
• Stimulate rate of axon myelinization

Question 18

What is the role of thyroid hormones on body growth?

Answer 18

Stimulate expression of gene for growth hormone in somatotrophs

Stimulate synthesis of many structural and enzymatic proteins

Promote calcification of bones

Question 19

What is the role of thyroid hormones for basal energy economy of the body?

Answer 19

Regulate basal rates of oxidative phosphorylation, body heat production, and Cygwin consumption (thermogenic effect)

Question 20

What is the role of thyroid hormone on intermediatory metabolism?

Answer 20

Stimulate synthetic and degradative pathways of carbohydrate, lipid, and protein metabolism

Question 21

How do thyroid hormones affect TSH secretion?

Answer 21

Inhibit TSH secretion by decreasing sensitivity of thyrotrophs to thyrotropin releasing hormone

Question 22

Describe parathyroid hormone secretion

Answer 22

Is a peptide hormone released from the parathyroid glands (chief cells) in response to low plasma Ca2+

Note: free Ca2+ in the plasma is the primary regulator of PTH

• The negative feedback relationship between plasma calcium and PTH secretion is highly sigmoidal, with steep portion representing the normal range of plasma free calcium. Free calcium is precisely regulated.
• to sense the free calcium, the parathyroid cells depend on high level of expression of calcium sensing receptors(CaSR)

Question 23

How does parathyroid hormone regulate calcium homeostasis?

Answer 23

The actions of parathyroid hormone (PTH):

1. Increase Ca2+ reabsorption in the distal tube
2. Inhibits phosphate Reabsorption in the proximal tubule of the kidney
3. Stimulates the 1-alpha-hydroxylase enzyme in the kidney, converting the inactive vitamin D to its active form [1, 25 di-OH D3]
4. Causes bone resorption, releasing Ca2+ and Pi into the blood

Question 24

What are the functions of 1,25-(OH)2Cholecalciferol (calcitriol)

Answer 24

Under normal conditions, Vit. D acts to raise plasma Ca2+ and phosphate. Thus, vitamin D promotes bone deposition. This is accomplished by:

1. Calcitriol increases the absorption of Ca2+ and phosphate by the intestinal mucosa by increasing the production of the Ca2+ binding protein calbindin. The details of this pr9cess are poorly understood
2. The resulting high concentrations of Ca2+ and phosphate in the Extracellular fluid exceed the solubility product, and precipitation of bone salts into bone matrix occurs.
3. Calcitriol enhances PTH’s action at the renal distal tubule

Question 25

Explain the regulation of Calcitriol secretion

Answer 25

-Vtiwmin D2 (ergocalciferol) is a vitamin and normally obtained from diet. It can be considered a prohormone. A slightly different form D3 (cholecalciferol) is synthesized in the skin After its conversion to 25-OH vitamin D3 in the liver, it can be stored in fat tissue Note: 25-OH vitamin D3 represent the best measure of body stores of vitamin D, when a deficiency is suspected Most of the 25-OH form, which is the immediate precursor for 1,25-OH vitamin D. Ultraviolet light also evokes skin tanning, decreasing penetration of UV light and thus decrease the subsequent formation of D3.