Lecture 1 Flashcards by T I

What does insulin do?

Regulates blood sugar levels | Binds to a receptor on the surface of liver, muscle and fat cells and activates a cell signalling pathway within those cells that promotes the translocation of glucose transporters to the cell membrane resulting in glucose uptake from the bloodstream

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What are hormones?

Chemical messengers released from one cell (or tissue) which produce a specific, receptor-mediated change in another cell (or tissue) | E.g insulin, TSH, cortisol

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What do hormones do?

Development: cell proliferation, growth and differentiation | Metabolism: energy storage, metabolic rate and body temperature | Fluid homeostasis: water balance, salt levels, blood volume and pressure | Reproduction: sexual maturation and behaviour, pregnancy and lactation

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What are glands?

Organ that synthesises and releases a substance into the bloodstream, body cavity or skin

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Which types of glands release substances into the bloodstream?

Endocrine

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Which types of glands release substances into the body cavity/skin?

Exocrine | Mucous | Serous | Sebaceous

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Give some examples of tissues with endocrine function and what they secrete

Kidney –> erythropoietin
Heart –> atrial natriuretic peptide
Gut –> Gastrin, secretin
Adipocytes –> leptin
Placenta –> lactogen

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Give some examples of cell to cell communication via hormones

Autocrine | Paracrine | Endocrine | Neurocrine

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What is autocrine signalling?

Cell A produces hormone | Cell A releases hormone | Cell A receives hormone

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What is paracrine signalling?

Cell A secretes hormone | Hormone acts on cell B | Cell B produces response

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What is endocrine signalling?

Cell A is a neurone | Cell A secretes hormone | Hormone enters bloodstream and acts on cell B | Cell B produces response

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What are the potential issues with endocrine signalling?

Takes a while to move through body in the bloodstream | Distance is longer

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What is neurocrine signalling?

Cell A is a neurone | Cell A secretes hormone | Hormone enters bloodstream and acts on cell B | Cell B produces response

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Give some examples of types of amino acid derived hormones

Single amino acid derivatives | Dipeptides | Small peptides | Intermediate-size particles | Complex polypeptides

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What are the 2 different types of hormones?

Amino acid derived
Lipid derived

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Give some examples of lipid derived hormones

Cholesterol derivatives | Fatty acid derivatives

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What are the two different hormone systems

peptide and catecholamines
steroid and thyroid hormones

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What are the properties of peptide and catecholamine hormones?

Rapid changes in plasma concentration
Plasma half-life: short (seconds to minutes)
Don’t readily cross cell membrane as they are made of amino acids –> Receptors need to be cell, membrane-bound receptors
Mechanism: activate preformed enzymes –> Secretory granules –> Constitutive + bursts
Speed of effect = rapid (seconds to minutes)

What are the properties of steroid and thyroid hormones?

Slow fluctuations in [plasma]
Plasma half-life: long (minute to days)
Type of receptors: intracellular
Mechanism: stimulate protein synthesis –> Direct rapid passage –> Related to secretion rate
Speed of effect: slow (hours to days)

Describe how endocrine systems work with glands

Stimulus (positive or negative) | 2. Stimulus acts on the glands | 3. Gland secretes hormone A (leads to concentration change of hormone A) | 4. Hormone A induces positive or negative effect on target tissue | 5. Target tissue exerts action or releases hormone B | 6. Hormone B acts on gland (usually negative)

How are peptide hormones synthesised?

Gene for protein/peptide is transcribed | 2. mRNA is transported to RER | 3. Translation of mRNA on rough ER | 4. Post-translational processing in golgi | 5. Packaging into secretory vesicles | 6. Exocytosis of peptide hormone

How are steroid hormones synthesised?

Hydrolysis of esters and release of cholesterol
Cholesterol is converted to pregnenolone by SCC enzyme in the mitochondria and transported to the smooth ER
Processing in the smooth ER
Diffusion of the steroid hormones

What is the process of peptide hormone cleavage? Use PTH as an example

N-terminal signal sequence directs the pre-pro-peptide hormone to the ER | 2. Signal sequence is cleaved in the ER and the pro-peptide that remains is glycosylated | 3. Endopeptidases then cleave pro-sequence to form mature secreted hormone

Give some examples of groups of steroid hormones

Glucocorticoids –> e.g cortisol
Mineralocorticoids –> e.g aldosterone
Androgens –> e.g testosterone
Oestrogens –> e.g oestradiol
Progestogens –> e.g progesterone

What is the key fact of steroid hormone synthesis?

All steroid hormones are derived from cholesterol | First step is always the same --> Cholesterol is converted to pregnenolone by cholesterol side-chain cleavage (SCC) enzyme which is a cytochrome P450

Give some examples of sites of steroid hormone synthesis

Adrenal cortex | Gonads | Placenta

What determines the specificity of where certain steroid hormones are produced?

Specificity of production depends on the enzymes required within the biosynthetic pathway | Certain enzymes are required for synthesis of certain hormones so those hormones can only be produced in the tissues where those enzymes are expressed

Where does the cholesterol come from for the synthesis of steroid hormones?

De novo synthesis (breakdown of acetyl CoA) LDL breakdown

How are circulating steroid hormones complexed?

Complexed with either albumen or steroid hormone binding proteins

What are the properties of albumen-steroid complexes?

Non-specific binding | Low affinity

What are the properties of steroid hormone binding protein complexes?

Specific | High affinity

What are the different types of steroid hormone binding proteins?

Sex steroid/androgen binding protein, e.g testosterone, estrodiol | Progesterone binding globulin, e.g progesterone | Corticosteroid binding protein, e.g cortisol, aldosterone

What are circulating steroid hormones? What do they do?

Inactive pool of hormones Protects against metabolic and chemical changes Buffers, by reversible dissociation, against sudden changes in active hormone concentrations

What are amino acid hormones derived from? How do you tell if a hormone is an amino acid hormone?

Derived from tyrosine/tryptophan | If a hormone name ends in '-ine', it is amino acid derived

What is a neuroendocrine axis?

Involves the brain Brain releases hormone/neurotransmitter (NT) Hormone/NT travels to pituitary gland and tells it to release hormone Pituitary gland hormone travels in bloodstream to another gland (e.g testes or thyroid) Other gland then releases another hormone that acts on brain and pituitary gland to regulate its release

What are releasing hormones?

Specifically reduce release of another hormone from the pituitary gland

What are tropic hormones?

Travel to and act on a target gland to influence the release of another hormone

What are trophic hormones?

Stimulate growth of a target tissue

Can hormones only be tropic or trophic?

They can be both | E.g growth hormone

What is the generic endocrine axis?

Outside factor/stimulus that is disrupting homeostasis initiates this reaction Stimulus signals to the hypothalamus and induces hypothalamus to: --> Secrete a releasing hormone --> Secrete an inhibiting hormone These hormones act on pituitary gland and stimulate release of tropic hormone Tropic hormone acts on target gland and stimulates release of new hormone New hormone acts on pituitary gland (short feedback loop) to reduce release of tropic hormone and on hypothalamus (long feedback loop) to reduce release of releasing/inhibiting hormone as stimulus is GONE New hormone also stimulates physiological effect on stimulus

What is required for hormones to act on target cells?

Hormone levels in circulation = low Hormone effects = mediated by specific, high affinity receptors Receptors can be present inside cell (e.g receptors for steroid/thyroid hormones) or on the cell membrane (peptide hormones) Linked to specific signal transduction pathways

What are endocrine disorders caused by?

* Excess/deficient secretion of a hormone * Failure to respond to a biologically active hormone (resistance) --> E.g insulin resistance --> key drive of Type 2 diabetes * E.g caused by too high or too low levels of hormone * Mechanisms vary --> often associated with chronic exposure to elevated levels of circulating hormone * Receptor malfunction is common

Give some examples of endocrine diseases and their causes

Diabetes (insulin deficiency or insensitivity) Thyroid disease (too little or too much TH) Infertility (hypothalamic, pituitary, gonadal) Obesity