Lecture 4 : Cellular Endocrine 1 Flashcards
What is endocrinology?
The study of hormones, their receptors and their intracellular signalling pathways
What are hormones and what type of signalling do they have?
Hormones are chemical messengers:
- Produced in one location by endocrine glands/cells
- Transported via the blood all over the body, to reach their target cells where they exert their effects
- Slower signals, generating slower, longer lasting responses (compared to neural signals)
What is a gland?
A bunch of hormone producing cells
What are the 3 classes of hormones? Are they lipid or water soluble?
- Peptide hormones (water soluble) - From 3 amino acids to large proteins
- Amine hormones - Derivatives of tyrosine (amino acid)
* Catecholamines (water soluble) - adrenaline & noradrenaline
* Thyroid hormones (lipid soluble) - Steroid hormones (lipid soluble) - Made from cholesterol
What is the chemical classification of water-soluble vs. lipid-soluble hormones?
Water-soluble:
* Mostly Peptides (75% of hormones)
* Some Amine hormones - catecholamines; adrenaline and noradrenaline
Lipid-soluble:
* Steroids
* Some amine hormones - thyroid hormones; T3 and T4
Describe the storage of water-soluble vs. lipid-soluble hormones:
Water-soluble:
* Made and stored until required
* Released by exocytosis
Lipid-soluble:
* Steroid hormones are made from cholesterol as required, and cannot be stored
* Thyroid hormones are made in thyroid cells and stored until required (This storage is unusual for lipid-soluble hormones)
Describe the transport of water-soluble vs. lipid-soluble hormones:
Water-soluble:
- Most peptide and all catecholamine hormones are transported dissolved in plasma
- Some peptide hormones are carried by specific binding proteins in the blood
Lipid-soluble:
- Steroid and thyroid hormones are transported in the blood bound to specific proteins
- A small fraction of these hormones are free and generally only this form can enter the target cell – i.e. only the free hormone is active
Free hormone + Binding protein -> Hormone protein complex
Where are the receptors for water-soluble vs. lipid-soluble hormones?
Receptors are proteins
Water-soluble:
- Outside or membrane-bound/on the surface of target cells
Lipid-soluble:
- Intracellular/inside the target cells
Describe the structure of peptide hormones:
Chains made of amino acids:
- Short peptide chains of only a few amino acids: Anti diuretic hormone (ADH)/Vasopressin
- Longer peptide chains, or more than 1 joined together: Insulin
- Proteins: Growth hormone
Describe the synthesis, storage and secretion of peptide hormones:
- Synthesis and cleavage: Preprohormone to Prohormone in the rER
- Packaging: Prohormone to hormone in the golgi apparatus
- Storage in vesicles: Hormone - water soluble (sometimes prohormone)
- Secretion by exocytosis: Hormone (and fragments) - sometimes prohormone
What is the structure of steroid hormones?
4 hydrocarbon rings
Describe the synthesis and secretion of steroid hormones:
- Stimulus: Another hormone binds to cell receptors, triggering a series of steps that lead to synthesis of the steroid hormone
- Synthesis: Cholesterol -> Steroid hormone
- Diffusion out of the cell: Hormone - lipid soluble
* must be bound to carrier proteins to travel in the blood
* cannot be stored
What is cortisol?
An adrenal steroid hormone which is synthesised in the adrenal cortex from cholesterol
- stress hormone
- a GLUCOcorticoid: mobilises glucose + other functions
What is aldosterone?
An adrenal steroid hormone which is synthesised in the adrenal cortex from cholesterol and corticosterone
- blood pressure hormone
- a MINERALcorticoid: control of kidney reabsorption of Na+, K+ and hydrogen ions (H+)
Name the 2 sex steroid hormones: What are they synthesised from?
- Testosterone
- Estradiol
Synthesised from cholesterol
Which enzyme converts testosterone into estradiol?
Aromatase
Give examples of catecholamines:
- Dopamine
- Norepinephrine
- Epinephrine
Thyroid hormones are also amines (made from tyrosine)
Describe the synthesis, storage and secretion of catecholamine hormones:
In the adrenal medulla
1. Synthesis: Tyrosine -> Dopamine
2. Synthesis: Dopamine -> Noradrenaline (norepinephrine)
3. Synthesis: Noradrenaline (norepinephrine) -> Adrenaline (epinephrine)
4. Storage in granules: Hormone; water soluble
5. Secretion by exocytosis: Hormone
What are the 2 thyroid hormones and what are they made from?
1.Triiodothyronine (T3)
2.Tetraiodothyronine (T4)
Made from tyrosine
Describe the synthesis, storage and secretion of thyroid hormones:
- Thyroglobulin (TGB) protein is made in thyroid follicles and contains tyrosine (Y)
- Iodine (I) enters follicle cell from blood and reacts with tyrosine in TGB
- Thyroid hormones detach from iodised TGB as needed
- T3 - the active form
- T4 - the more plentiful form
- T3 and T4 travel bound to a carrier protein (thyroid-binding globulin, TBG) to target cells
Note: Iodine is a necessary part of our diet as it is required for the production of thyroid hormone
Describe the fate of secreted hormones:
- Endocrine cell secretes hormone
↓ - Hormone circulating in blood
↓ - Excreted in urine or feces; Inactivated by metabolism; Activated by metabolism; Bind to receptor and produce cellular response on target cells
↓ - Inactivated by metabolism -> excreted in urine or feces
↓ - Activated by metabolism -> bind to receptor and produce cellular response on target cells
↓ - Hormone unbinds
↓ - Excreted in urine or feces; Inactivated by metabolism
What is hormone specificity?
- A hormone only causes a response in cells that have a receptor for that hormone
- Different types of cells can have receptors for the same hormone
BUT - The response caused by the hormone binding to the receptor can be different for the different types of cells
What is hormone target cell sensitivity?
- The sensitivity of a target cell to any particular hormone depends on the number of receptors expressed
- The more receptors for a hormone that a cell has, the greater the likelihood that hormone will bind to one of them, causing a response
How is target cell sensitivity regulated?
Regulation of the number of receptors is a homeostatic mechanism to return the cell response to normal even when the level of the hormone varies
Up-regulation:
- Synthesis > degradation
- ↑ the number of receptors expressed to ↑ sensitivity
- Occurs when the cell is exposed to LOW levels of the hormone for a long period of time
Down-regulation:
- Synthesis < degradation
- ↓ the number of receptors expressed to ↓ sensitivity
- Occurs when the cell is exposed to HIGH levels of the hormone for a long period of time
