Chapter 74 Introduction To Endocrinology

Question 1

Which 3 general classes of hormones exist?

Answer 1

Proteins and polypeptides
Steroids
Derivates of the amino acid tyrosine

Question 2

Where are protein and peptide hormones synthesised?

Answer 2

On the rough end of the endoplasmic reticulum of the different endocrine cells. These are then transferred to the Golgi apparatus for packaging into secretory vesicles. In this process, enzymes in the vesicles cleave the prohormones to produce smaller biologically active hormones and inactive fragments. Secretion of the hormones occurs when the secretory vesicles fuse with the cell membrane and the granular contents are extruded into the interstitial fluid or directly into the bloodstream by exocytosis.

Question 3

Are peptide hormones water soluble?

Answer 3

Yes - this allows them to enter the circulatory system easily where they are carried to their target tissue.

Question 4

What are steroid hormones synthesised from?

Answer 4

Cholesterol

Question 5

What two groups of hormones are derived from tyrosine?

Answer 5

The thyroid and the adrenal medullary hormones

They are formed by the actions of enzymes in the cytoplasmic compartments of the glandular cells.

Question 6

How are the thyroid hormones synthesised and stored?

Answer 6

Synthesised and stored in the thyroid gland and incorporated into macromolecules of the protein thyroglobulin which is stored in large follicles within the thyroid gland.

Question 7

What happens to thyroid hormones when they are released into the blood?

Answer 7

Combine with plasma proteins especially thyroxine binding globulin which slowly releases the hormones to the target tissue.

Question 8

What does ADH do?

Answer 8

Increases water reabsorption by the kidneys and causes vasoconstriction and increased blood pressure.

Question 9

What does calcitonin do?

Answer 9

Promote deposition of calcium in the bones and decreases extracellular fluid calcium ion concentration.

Question 10

What does aldosterone do?

Answer 10

Increases renal sodium reabsorption, potassium secretion and hydrogen ion secretion.

Question 11

How are catecholamines released from the adrenal medullary cells?

Answer 11

By exocytosis

Question 12

How are water soluble hormones (peptides and catecholamines) transported in the blood?

Answer 12

They are dissolved in the plasma and transported from their sites of synthesis to target tissues where they diffuse out of the capillaries into the interstitial fluid and ultimately to target cells.

Question 13

What is the metabolic clearance rate?

Answer 13

Rate of disappearance of hormone from the plasma / concentration of hormone

Question 14

How are hormones cleared from the plasma?

Answer 14

1. Metabolic destruction by the tissues
2. Binding with the tissues
3. Excretion by the liver into the bile
4. Excretion by the kidneys into the urine

Question 15

Which hormones are fastest degraded - the water soluble or the hormones that are bound to plasma proteins?

Answer 15

Hormones that are bound to plasma proteins are cleared from the blood at much slower rates.
Water soluble hormones are usually degraded by enzymes in the blood and tissues and rapidly excreted by the kidneys and liver.

Question 16

Where are the locations for the different types of hormone receptors?

Answer 16

1. In or on the surface of the cell membrane
2. In the cell cytoplasm
3. In the cell nucleus

Question 17

What can down regulation of receptors occur as a result of?

Answer 17

1. Inactivation of some of the receptor molecules
2. Inactivation of some of the intracellular signaling molecules
3. Temporary sequestration of the receptor to the inside of the cell
4. Destruction of the receptors by lysosomes after they are internalised
5. Decreased production of the receptors

Question 18

How does G protein linked hormone receptors work?

Answer 18

When the ligand (hormone) binds to the extracellular part of the receptor - a conformational change occurs in the receptor that activates the G proteins and induces intracellular signals that either
1. Open or close cell membrane ion channels
2. Change the activity of an enzyme in the cytoplasm of the cell

When the hormone activates the receptor, the inactive a, b and gamma G protein complex associates with the receptor and is activated with and exchange of GTP for GDP. This causes the a subunit (to which GTP is bound) to dissociate from the B and gamma subunits of the G protein and to interact with membrane bound target proteins that initiate intracellular signals.

Question 19

How does en enzyme linked hormone receptor work? Give an example of an enzyme linked hormone receptor.

Answer 19

When the hormone binds to the extracellular part of the receptor, an enzyme immediately inside the cell membrane is activated.

One example is the leptin receptor.

Question 20

What is cAMP?

Answer 20

Its a second messenger. It’s not the hormone itself that directly institutes the intracellular changes but the cAMP serves as a second messenger to cause these effects.

The hormone binds with a special transmembrane receptor which then becomes the activates enzyme adenyl cyclase at the end that protrudes to the interior of the cell. This cyclase catalyses the formation of cAMP.

Question 21

Give examples of hormones that use intracellular hormone receptors and activation of genes?

Answer 21

Adrenal and gonadal steroid hormones, thyroid hormones, retinoid hormones and vitamin D bind with receptors inside the cell rather than in the cell membrane. These hormones are lipid soluble and cross the cell membrane and interact with receptors in the cytoplasm or nucleus.

The activated hormone receptor complex then binds with a specific regulatory (promoter) sequence of the DNA called the hormone response element and in this manner either activates or represses transcription of specific genes and formation of messenger RNA.

Question 22

cAMP is not the only second messenger used by different hormones. Name two other especially important ones?

Answer 22

1. Calcium ions and associated Calmodulin
2. Products of membrane phospholipid breakdown

Question 23

Which hormones use the Adenylyl Cyclase - cAMP second messenger system?

Answer 23

ACTH
Angiotensin II
Calcitonin
Catecholamines
Corticotropin releasing hormone
FSH
Glucagon
LH
PTH
Secretin
Somatostatin
TSH
Vasopressin

Question 24

Name hormones that use the phospholipase C second messenger system?

Answer 24

Angiotensin II (vascular smooth muscle)
Catecholamines (a receptors)
GnRH
Growth hormone releasing hormone
Oxytocin
Thyrotropin releasing hormone
Vasopressin (V1 receptor, vascular smooth muscle)

Question 25

One second messenger system operates in response to the entry of calcium into the cells. What is calcium entry initiated by?

Answer 25

1. Changes in membrane potential that open calcium channels
2. Hormone interacting with membrane receptors that open calcium channels

When entering the cell, calcium ion bind with the protein calmodulin. This protein has four calcium sites and when 3 or 4 of these sites have bound with calcium - the calmodulin changes its shape and initiates multiple effects in the cell.

Question 26

Describe how it works when steroid hormone increase protein synthesis?

Answer 26

1. The steroid hormone diffuses across the cell membrane and enters the cytoplasm of the cell where it binds with a specific receptor protein.
2. The combines receptor- hormone then diffuses into or is transported into the nucleus.
3. The combine binds at specific points on the DNA strands in the chromosomes which activates the transcription process of specific genes to form mRNA.
4. The mRNA diffuses into the cytoplasm where it promotes the translation process at the ribosomes to form new proteins.

Question 27

Thyroid hormones increase gene transcription in the cell nucleus. What are two important features of thyroid hormone function in the nucleus?

Answer 27

1. They activate the genetic mechanisms for the formation of many types of intracellular proteins - probably 100 or more. Many of these enzymes that promote enhanced intracellular metabolic activity in virtually all cells of the body.
2. Once bound to the intranuclear receptors, the thyroid hormones can continue to express their control functions for days or even weeks.

Question 28

What are the receptors called that the thyroid hormones bind to in the nucleus?

Answer 28

Activated transcription factors located within the chromosomal complex and they control the function of the gene promoters.