LECTURE 1 (Introduction to endocrinology)

Question 1

What are the different types of chemical messenger systems?

Answer 1

• Neurotransmitters = released by axon terminals of neurons into synaptic junctions + act locally to control nerve cell function
• Endocrine hormones = released by glands/specialised cells into circulating blood + influence function of target cells at another location
• Neuroendocrine hormones = secreted by neurons into circulating blood + influence function of target cells at another location
• Paracrine = secreted by cells into extracellular fluid + affect neighbouring target cells of a different type
• Autocrines = secreted by cells into extracellular fluid + affect the same cells that produced them
• Cytokines = peptides secreted by cells into the extracellular fluid + can function as autocrines, paracrines or endocrine hormones

Question 2

How does the pituitary gland secrete hormones in response to neural stimuli?

Answer 2

1) Neuroendocrine cells located in the hypothalamus have axons that terminate in the POSTERIOR PITUITARY GLAND and MEDIAN EMINENCE
2) Hypothalamus secretes neurohormones (ADH, oxytocin, hypophysiotropic hormones) which control the secretion of anterior pituitary hormones

Question 3

What are the three general classes of hormones?

Answer 3

• Proteins and polypeptides
  [hormones secreted by anterior + posterior pituitary gland, pancreas and parathyroid gland]
• Steroids
  [secreted by adrenal cortex, ovaries, testes and the placenta]
• Derivatives of the amino acid tyrosine
  [secreted by the thyroid and adrenal medulla]

Question 4

Describe how Protein hormones are synthesised

Answer 4

1) Protein and peptide hormones synthesised on the ROUGH END OF THE ENDOPLASMIC RETICULUM of the different endocrine cells. Usually synthesised first as non-biologically active, larger proteins (PREPROHORMONES)
2) Preprohormones are cleaved into smaller PROHORMONES and inactive fragments and are transferred to the GOLGI APPARATUS for packaging into secretory vesicles
3) Vesicles are stored within the cytoplasm and are bound to the cell membrane until their secretion is needed

Question 5

Describe how protein hormones are released

Answer 5

THE 2 DIFFERENT STIMULUS FOR EXOCYTOSIS
- Increase in cytosolic calcium concentration caused by depolarisation of the plasma membrane
- stimulation of an endocrine cell surface receptor causes increased cyclic adenosine monophosphate (cAMP) -> activates protein kinases that initiate secretion of the hormone

Peptide hormones are WATER SOLUBLE -> allows to enter circulatory system where they are carried to their target organs

Question 6

How are steroid hormones synthesised?

Answer 6

• Consist of three CYCLOHEXYL RINGS and one CYCLOPENTYL RING
• synthesised from cholesterol (from cytoplasm + de-novo synthesis of cholesterol in steroid-producing cells)
• Highly lipid soluble -> once synthesised, diffuse across cell membrane and enter the interstitial fluid then blood

Question 7

How are the Amine hormones synthesised?

Answer 7

Thyroid and Adrenal medullary hormones are
- derived from tyrosine
- formed by actions of enzymes in cytoplasm of glandular cells

THYROID HORMONES:
1) synthesised + stored in thyroid gland and incorporated into THYROGLOBULIN (stored in large follicles within thyroid gland)
2) Thyroglobulin splits, releasing free hormones into blood stream
3) After entering blood, combine with plasma proteins (e.g thyroxine-binding globulin which slowly releases hormones to target tissues)

EPINEPHRINE & NOREPINEPHRINE:
1) Taken up into preformed vesicles and stored until secreted
2) Released from adrenal medullary cells by exocytosis
3) Once in circulation, can exist in plasma in free form or in conjugation with other substances

Question 8

What works faster, Epinephrine & Norepinephrine or Thyroid hormones?

Answer 8

Epinephrine & Norepinephrine

Explanation: E&N are secreted within seconds after gland is stimulated whereas Thyroid hormones may require months for full effect. This is because E&N are water-soluble and have a short half-life whereas Thyroid hormones bind to plasma proteins and last longer.

Question 9

What does “The controlled variable is the degree of activity of the target tissue” mean?

Answer 9

Only when the target tissue activity rises to an appropriate level will feedback signals to the endocrine gland become powerful enough to slow further secretion of the hormone

Question 10

What causes cyclical variations in hormone secretion?

Answer 10

Changes in activity of neural pathways involved in controlling hormone release

Explanation: Cyclical variations are influenced by seasonal changes, various stages of development and ageing, sleep.

Question 11

Which hormones are water-soluble?

Answer 11

Peptides and Catecholamines

Question 12

What is the difference in the transport between water-soluble and lipid-soluble hormones?

Answer 12

Water soluble = dissolved in plasma and transported from their sites of synthesis to target tissues -> diffuse out of capillaries, into interstitial fluid and to target cells

Lipid soluble = bound to plasma proteins and serve as reservoirs (replenish the concentration of free hormones when bound to target receptors or lost from circulation)

Question 13

What are the two factors that can increase or decrease the concentration of a hormone in the blood?

Answer 13

• Rate of hormone secretion into the blood
• Rate of removal of the hormone from the blood (METABOLIC CLEARANCE RATE)

Question 14

What is the calculation for Metabolic clearance rate?

Answer 14

Metabolic clearance rate = Rate of disappearance of hormone from the plasma / Concentration of hormone

Question 15

What are the different ways hormones are “cleared” from the plasma?

Answer 15

• Metabolic destruction by the tissues
• Binding with the tissues
• Excretion by the liver into the bile
• Excretion by the kidneys into the urine

Question 16

Where can the different types of hormone receptors be found?

Answer 16

• In or on the surface of the cell membrane [protein, peptide and catecholamine]
• In the cell cytoplasm [steroid]
• In the cell nucleus [thyroid]

Question 17

What can cause down-regulation of receptors?

Answer 17

• Inactivation of some receptor molecules
• Inactivation of some of the intracellular protein signalling molecules
• Temporary sequestration of the receptor to the inside of the cell wall (away from where hormones can bind to them)
• Destruction of the receptors by lysosomes
• Decreased production of the receptors

Question 18

What is “Up-regulation” of receptors and intracellular signalling proteins?

Answer 18

Stimulating hormone induces greater than normal formation of receptor or intracellular signalling molecules or greater availability of the receptor for interaction with the hormone

EFFECT: The target tissue becomes progressively more sensitive to the stimulating effects of the hormone

Question 19

Describe how G-proteins work

Answer 19

1) Hormone binds to extracellular part of receptor and conformational change occurs in receptor
2) GDP-bound trimeric G protein associates with the cytoplasmic part of the receptor to exchange GDP for GTP
3) Displacement of GDP to GTP causes alpha subunit to dissociate from trimeric complex and associate with intracellular signalling proteins which alter activity of ion channels/intracellular enzymes
4) When hormone removes, alpha subunit inactivates by converting GTP to GDP and joins beta and gamma subunits again

Question 20

What does the activated hormone-receptor complex bind to in intracellular hormone activation?

Answer 20

Hormone response element (in the DNA)

Question 21

What are the different second messengers used by different hormones?

Answer 21

• cAMP
• Calcium ions and associated calmodulin
• Products of membrane phospholipid breakdown

Question 22

Describe the Adenylyl Cyclase-cAMP second messenger system

Answer 22

1) Hormone binds to receptor, allowing coupling of the receptor to a G protein
2) Stimulation of adenylyl cyclase (membrane-bound enzyme) by Gs protein catalyses the conversion of cytoplasmic ATP into cAMP
3) cAMP activates cAMP-dependent protein kinase which phosphorylates specific proteins that trigger a cascade of enzymes to carry out function

Question 23

What is calcium entry into cells initiated by?

Answer 23

• Changes in membrane potential that open calcium channels
• A hormone interacting with membrane receptors that open calcium channels

Question 24

How do Steroid hormones work?

Answer 24

1) Steroid hormone diffuses across the cell membrane and enters the cytoplasm of the cell where is binds with a specific receptor protein
2) The combines receptor protein-hormone diffuses into or is transported into the nucleus
3) The combination 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 25

What do Thyroid hormones do?

Answer 25

Increase gene transcription in the cell nucleus

Question 26

Describe the process of Radioimmunoassay

Answer 26

1) Antibody highly specific for the hormone to be measured is produced
2) Small quantity of antibody is
- mixed with a quantity of fluid from animal containing hormone to be measured
- mixed simultaneously with purified standard hormone that has been tagged with radioactive isotope
3) Natural hormone and radioactive hormone compete for the binding sites of the antibody

Large amount of radioactive hormone bound to antibody = only a small amount of natural hormone to compete with the radioactive hormone -> small concentration

Small amount of radioactive hormone bound to antibody = large amount of natural hormone to compete for binding sites

Question 27

What condition must be met in Radioimmunoassay?

Answer 27

There must be too little antibody to bind completely both the radioactive tagged hormone and the hormone in the fluid to be assayed