Lecture 06 - Hormone Synthesis And Action

Question 1

What is intracrine signalling?

Answer 1

1. Generated by a chemical acting within the same cell

Question 2

What is autocrine signalling?

Answer 2

1. Signals where a chemical acts in the same cell

Question 3

What is paracrine signalling?

Answer 3

1. Chemical communication between adjacent cells in a tissue/organ

Question 4

What is endocrine/neuroendocrine signalling?

Answer 4

1. Chemicals released by specialised cells into circulation to act on a distant target tissue

Question 5

What are the differences between endocrine and nervous tissue?

Answer 5

1. Chemical coordinator:
   E: hormone - many different types each affecting different specific tissue
   N: NT - few types, secreted only into target tissue
2. Speed of effect:
   E: generally slow
   N: generally rapid
3. Duration of effect:
   E: generally long-lasting
   N: generally short-lived
4. Localisation if effect:
   E: secreted into blood therefore widespread
   N: secreted into target cell so effect very localised
5. Boundaries become blurred as some hormones are secreted from nerve endings (neuroendocrine)

Question 6

What is endocrinology?

Answer 6

1. Endocrinology is the study of hormones
2. These are substances secreted into the blood by specialised cells in glands
3. They are carried in the blood to receptors on target organs (via endocrine, autocrine, paracrine)
4. Present in minute concentrations and bind to receptors to influence cellular reactions

Question 7

What are endocrine glands?

Answer 7

1. Release secretions (hormones) into blood directly from cells (apart from paracrine), ductless

Question 8

Why are exocrine glands?

Answer 8

1. Release secretions outside the body, may be ducted

Question 9

What are mixed glands?

Answer 9

1. Mixture of endocrine and exocrine, occurs in pancreas which produces digestive juice as well as insulin, glucagon and somatostatin

Question 10

How are hormones controlled?

Answer 10

1. Feedback is the process by which the body senses change and responds it
2. Negative - most common, the body senses change and activates mechanisms to reduce it
3. Positive - process by which body senses change and activates mechanisms to amplify it

Question 11

What is an endocrine axis?

Answer 11

1. The target tissue for a hormone may be another endocrine gland (via tropic hormone)
2. The functional grouping of endocrine glands is called an endocrine acid
3. Faults may occur along the axis

Question 12

What is the hypothalamo-pituitary axis? I

Answer 12

1. TRH released by hypothalamus
2. This stimulates anterior pituitary to release TSH
3. This binds to receptors in the thyroid gland
4. This stimulates secretion of T3 and T4
5. This affects cells of the body
6. When blood concentrations of the hormones increase above a set level, TRH secretion is inhibited
7. Example of negative feedback

Question 13

What are the three main groups of hormones?

Answer 13

1. Protein/peptide hormones
2. Steroid hormones
3. Amine hormones

Question 14

How do peptide hormones work?

Answer 14

1. Most common type of hormone
2. Hydrophilic so doesn’t need to be carried in the blood
3. Stores in membrane bound vesicles for release via exocytosis
4. Produced on ribosomes (rER) as a large precursor molecule (pre-hormone)
5. Pre-hormone is converted to prohormone and then to hormone
6. May be transported to Golgi in certain cases

Question 15

How is insulin, a peptide hormone, produced?

Answer 15

1. A large precursor allows structural specificity.
2. Signal peptide is cleaved and covalent S-S bonds are formed. Preproinsulin becomes proinsulin.
3. Proinsulin is further cleaved into a C-peptide and insulin.
4. Endoprotease PC2 and PC3 and carboxypeptidase involved.

Question 16

How do steroid hormones work?

Answer 16

1. Steroid hormones are all made from cholesterol, and have a four ring structure.
2. Are made in the adrenal cortex.
3. Are lipid soluble.
4. Synthesised as required, and diffuse out of the cell.
5. Synthesised in sER from cholesterol, derived from diet or acetate.

Question 17

How are steroid hormones formed?

Answer 17

1. The first and RDS is the conversion of cholesterol to pregnenolone.
2. Formed in the mitochondrion.
3. Moves to the sER for processing to hormones.
4. Hormones then diffuse out of the cell.
5. Enzymes are important in determining what structure is formed from pregnenolone.

Question 18

Where are hormones formed?

Answer 18

1. Tissue-specific and cell-specific expression of enzymes occur in each layer for a particular hormone.
2. Glomerulosa - aldosterone
3. Fasciculata - cortisol
4. Reticularis - adrenal androgens
5. Means other layers don’t express the enzymes necessary for synthesis of other enzymes.

Question 19

How are steroid hormones secreted and excreted?

Answer 19

1. Steroid hormones are rapidly excreted from the cell, with little or no storage.
2. Increases in secretion mean increase in rate of synthesis.
3. Steroid hormones are eliminated by excretion in urine or bile, or by inactivating metabolic transformations.

Question 20

What are amine hormones?

Answer 20

1. Include thyroid hormones
2. Are lipid-soluble
3. Derived from tyrosine
4. T4 and T3 contain 4 and 3 iodine atoms.
5. Are small and non-polar molecules, this soluble in plasma membrane

Question 21

How is T3 and T4 synthesised in the thyroid?

Answer 21

1. Produced from thyroid follicular cells within the thyroid gland.
2. Process regulated by TSH secreted from anterior pituitary.
3. Thyroglobulin produced by TFCs before being secreted and stored in the follicular lumen.
4. Iodide and sodium co-transported into the cell, and concentrated in the TFCs.
5. React with enzyme thyroperoxidase, where iodine is bound to tyrosine residues in thyroglobulin molecules to form MIT and DIT.
6. Two DIT produces T4. One MIT and DIT makes T3.
7. Proteases digest iodinated thyroglobulin, releasing T4 and T3 by exocytosis.
8. T4 is a prohormone and a reservoir for more active, main thyroid hormone T3, and is converted as needed in tissues.

Question 22

How are hormones transported in the blood?

Answer 22

1. Peptide hormones are freely water soluble, so travel in the blood.
2. Steroid and thyroid hormones need to be transported in blood by carrier proteins.
3. This increases their solubility in blood, half life and creates accessible reserves.

Question 23

What are the properties of the carrier proteins?

Answer 23

1. Can be specific e.g. TBG (thyroid binding globulin) or CBG (cortisol binding globulin)
2. Or non-specific e.g. albumin, generally binds aldosterone and is loose-binding
3. Bound (inactive) and free hormones (active) are in equilibrium

Question 24

Where do the hormones work?

Answer 24

1. Peptide hormones - cell surface receptors

2. Steroid and thyroid - intracellular receptors

Question 25

What is the cellular action of peptide hormones?

Answer 25

1. Bind to receptor on cell surface 2. Activates second messenger cascade e.g. cAMP 3. Phosphorylation of proteins causes activation, which causes a change in cellular function

Question 26

What is the cellular action of steroid and thyroid hormones?

Answer 26

1. Receptors are within the cytoplasm of target cell (intracellular receptors) 2. Belong to a family of receptors = steroid/thyroid hormone receptor superfamily 3. Hormone-receptor complex binds to specific hormone response elements in the promoter region of specific genes 4. Modifies gene transcription and protein synthesis 5. Therefore, receptors are described as ligand-inducible transcription factors

Question 27

What is the mode of action?

Answer 27

1. The mode of action is determined by its chemistry 2. Lipophobic, water soluble hormones act on surface receptors 3. Lipophilic, lipid soluble hormones act on intracellular receptors

Question 28

Where do endocrine disorders arise from?

Answer 28

1. Overproduction of a hormone 2. Underproduction of a hormone 3. Non-functional receptors that cause target cells to become insensitive

Question 29

Where does endocrine knowledge come from?

Answer 29

1. Clinical observation and experiments

Question 30

What are the causes and treatments of endocrine disorders?

Answer 30

1. Excess of hormone - often caused by tumours, can be caused by exogenous administration of hormone + treated by surgical removal of part of gland 2. Deficiency - primarily caused by lack of response from organ to tropic hormone, second cause from lack of tropic hormone, due to autoimmune organ destruction + treatment - replacement therapy (thyroid and steroid orally, insulin, GH, peptide via injection as otherwise degraded) 3. Failure can happen at any point from synthesis, to the receptor level, or cascade generation

Question 31

What disorders result from deficiency or excess?

Answer 31

1. Growth hormone D - GHD, dwarfism E - Gigantism (child), acromegaly (adult) 2. ADH D - diabetes insipidus E - hypervolaemia (SIADH) 3. Thyroid D - hypothyroidism, hashimoto's thyroiditis, congenital hypothyroidism (iodine def.) E - hyperthyroidism (Grave's disease) 4. Parathyroid D - Hypoparathyroidis - tetany E - hyperparathyroidism bone resorption 5. Insulin D - diabetes mellitus E - coma 6. Cortisol D - adrenal insufficiency (Addison's disease) E - Cushing's syndrome 7. Aldosterone D - hypoaldosteronism E - Conn's aldosteronism