Introduction to the Endocrine System

Endocrine definition

relating to or denoting glands which secrete hormones or other products directly into the blood

Exocrine definition

A gland that makes substances such as sweat, tears, saliva, milk, and digestive juices, and releases them through a duct or opening to a body surface.

What is included in the Endocrine system - give some examples

Hypothalamus

brain region controlling the pituitary gland

pituitary gland

secretes many different hormones, some of which affect other glands

Pineal gland

Secretes melatonin and helps establish circadian rhythms

Thyroid glands

affects metabolism, among other things - iodine is in the chemical structure

Parathyroids gland (embedded through the thyroid gland)

help regulate the level of calcium in the blood

Adrenal glands

helps trigger fight or flight response

e.g. adrenaline and noradrenaline amongst other hormones

Pancreas

-Regulates the level of sugar in the blood

-Secretes insulin, glucagon

-located behind the stomach

Testis

secretes male sex hormones

Ovary

secretes female sex hormones

What are the 4 functions of the Endocrine system?

- Development: proliferation, growth, differentiation, organogenesis

- Reproduction: sexual maturation & behaviour, maintenance of

pregnancy, lactation

- Metabolism: carbohydrate, energy storage, metabolic rate,

temperature

- Homeostasis: water balance, salt levels, blood volume & pressure

How does the endocrine system work?

- Hormones are the messenger molecules of the endocrine system - they work by altering the structure and/or activity of the target cell

by binding to specific hormone receptors

- Examples:- stimulating DNA synthesis, affecting

transcription/translation of mRNAs (sex hormones), affecting channel proteins &

enzymes by modifying their shape (e.g. catecholamines)

- Helps to maintain homeostasis- a constant internal environment (all feedback loops used for this)

What is a hormone?

- a substance secreted by the cells of endocrine

glands/tissues that regulates the activity of other cells in the body

- Hormones are released into the blood stream, transported to their distant target cells in the blood and act on these target cells via

specific receptors

- Different target cells express receptors for different hormones

What are the different types of hormone?

- Amino acid-derived (e.g. Catecholamines: adrenaline and noradrenaline)

-Peptide - short and/or long chains of amino acids (e.g. insulin)

-Lipid-derived - derived from lipids such as cholesterol (steroid) or arachidonic acid (eicosanoids) e.g Testosterone and Progesterone

What are amino acid derived hormones?

- Amino acid derived hormones are structurally based on one of two

amino acids: Tyrosine or Tryptophan

- Tyrosine-based hormones:

o Thyroid hormones e.g., T3, T4 both produced by thyroid

glands

o Catecholamines e.g., adrenaline (epinephrine) , noradrenaline (norepinephrine), dopamine

Note: both Thyroxine and adrenaline have similar structures to amino acid tyrosine as shown in image attached - hence why they are tyrosine amino acid derived hormones

- Tryptophan-based hormones:

o Melatonin produced by the pineal gland

Image for structure of tryptophan (amino-acid - anything based works on surface receptors)-based hormone melatonin

Structural similarity between melatonin and tryptophan (an amino acid) showing it is a amino acid derived hormone

How do amino-acid-derived hormones trigger responses?

- All amino-acid derived hormones but thyroid

hormones bind to cell membrane receptors

- Activation of the receptor triggers the appearance of

second messengers (cAMP - write the long version of these secondary messengers, cGMP or Ca) in the cytoplasm which

then triggers the hormone response

Kinase enzyme group

The addition of a phosphate

Phosphotase group

The subtraction of a phosphate

How does thyroid hormone act differently to trigger responses in comparison to other amino acid derived hormones ?

- Thyroid hormone acts differently as it can cross the plasma

membrane via diffusion or a transport protein

- It binds to intracellular (cytoplasmic) receptors which triggers

transcription and mRNA production

- OR it binds to receptors at the mitochondria which increases ATP

Transcription

the process of making a messenger RNA (mRNA) copy of a DNA sequence

What are peptide hormones?

- Peptide hormones are hydrophilic, able to interact with cell

membrane receptors & can be:

o Peptides: oxytocin, ADH

o Polypeptides: insulin, growth hormone

o Glycoproteins (follicle stimulating hormones): LH, FSH, TSH

Peptides won't act in the cytoplasm as they are too big

What are the two pathways in which peptide hormones can be

secreted?

- 1) Regulated secretion: the cell stores hormone in secretory

granules and released them in bursts when stimulated e.g. insulin triggered by an increase of glucose in the blood

Mechanism:

1) Insulin is synthesised in the beta cells of the pancreas in insulin secreting granules

2) Upon increase of blood glucose levels, glucose enters the pancreas beta cells via glucose transporters where it will be metabolised which will cause the release of ATP

3) This increase in ATP will close ATP sensitive K+ channels which will change the electronic charge of the cell membrane

4) This allows the voltage sensitive calcium channel to be opened - calcium moves into the beta cells via diffusion = phosphorylation of various proteins (insulin receptor substrates) which allows the insulin in the granules to be fused onto the cell membrane and then released into the blood

- 2) Constitutive secretion: the cell does not store hormone but

secretes it from secretory vesicles as it is synthesised e.g., FSH (follicle-stimulating hormone) or testosterone

Amino acid hormones

Based on Tryptophan and tyrosine

Steroid hormones

based on cholesterol

What are lipid-derived hormones (four ring structure) - e.g. sex hormones or cortisol hormones?

- Lipid derived hormones are derived from lipids such as

cholesterol (steroid) or arachidonic acid (eicosanoids)

- Lipid-derived hormones are lipophilic meaning they can enter the cell by crossing the plasma membrane; they then bind to

intracellular cytoplasmic receptors and regulate gene transcription

by binding to hormone-response elements in DNA

- Example: Testosterone stimulates the production of structural

proteins in skeletal muscle fibres which increase muscle size and

strength

Explain what we mean when we describe a cell as a target cell for a particular hormone.

A cell is a target cell because it has a specific receptors for a given

hormone

What are the 2 different types of hormone receptors?

-Cell membrane receptors

-Intracellular receptors

List and describe the 3 features of Cell membrane receptors

o Extracellular domains (hydrophillic) are residues exposed to the outside

of the cell and interact with the hormone

o Transmembrane domains are hydrophobic stretches of

amino acids found within the lipid bilayer and anchor the

receptor in the membrane

o Intracellular domains are parts of the receptor within the

cytoplasm and respond to hormone binding by activating

second messengers, opening ion channels and activating

enzymes

List and describe the 2 types of Cell membrane receptors

o Enzyme-linked/catalytic receptors whereby a binding of an

extracellular ligand causes enzymatic activity on the

intracellular domain e.g., insulin receptor, tyrosine kinase

receptor (tyrosine will be responsible for phosphorylating insulin receptor substrates)

o G-protein coupled receptors like Glucagon-like peptide 1

are either excitatory or inhibitory and involve second

messengers

Diagram for above - GPCR

Where are intracellular receptors located and how does feedback control of hormone secretion take place here?

-Located either in cytoplasm or nucleus (within the cell membrane)

- External stimulus activates the endocrine cell (this stimulus is

specific for the endocrine cell type)

- The endocrine cell releases hormone into the blood (hormones are

rapidly cleared from circulation via liver/kidney)

- The response reduced the stimulus as part of a negative feedback

control loop to ensure homeostasis

Describe feedback control of insulin secretion from pancreatic

beta cells

- An increase in plasma glucose concentration is the external

stimulus

- The increase in plasma glucose concentration activates insulin-

secreting cells which increases insulin secretion

- This increase in insulin secretion increase plasma insulin

concentration

- The increase in plasma insulin concentration enables insulin to

reach its target cells consequently increasing the actions of insulin

to transport glucose from plasma to inside cells via glucose transporters = reduces the

stimulus of increased plasma glucose

What is the difference between negative and positive feedback

loops?

- Negative feedback involves the response counteracting the

stimulus by shutting off the response loop e.g., TSH (Thyroid stimulating hormone) produces T3

and T4 & T3 and T4 negatively affect TSH production

- Positive feedback involved the response reinforcing the stimulus

sending the parameter further from the setpoint and requires an

outside factor to shut off the feedback cycle e.g., more oxytocin release when more contraction of the uterus during

parturition (childbirth)

Oxytocin

a hormone that plays a role in many aspects of human behaviour and reproduction

What is meant by long and short feedback loops?

-The secretion of hormones are regulated via feedback loops (mostly negative)

-The response can involve multiple organs

Example:

When the Hypothalamus releases Cortical Releasing Hormone (CRH - a protein), this triggers the Anterior Pituitary to release Adrenocorticotropic hormone (ACTH) which triggers the Adrenal Cortex to release Cortisol.

Cortisol can generate a negative feedback loop to switch of the release ACTH.

At the same time, Cortisol can also feedback to the hypothalamus to switch off the release of CRH, which is described as a long feed back loop because it involves 3 endocrine organs (Hypothalamus, Anterior pituitary and the Adrenal cortex)

Note:

ACTH can also feedback to the Hypothalamus to switch off the release of CRH which is also a short negative feedback loop

-Can be controlled in a more controlled way

What is the result of homeostatic controls?

- Successful control = homeostasis established

- Failure to control = illness and/or death

List and describe some disorders of the endocrine systems - feedback loops out of sync

- Excessive hormone secretion- acromegaly (a rare condition where the body produces too much growth hormone, causing body tissues and bones to grow more quickly), giantism due to too

much growth hormone and Cushing’s syndrome due to too much

cortisol;

- Deficient hormone secretion-Type 1 Diabetes due to no insulin,

Addison’s disease due to lack of adrenal cortisol, thyroid insufficiency

- Failure to respond to a hormone-Type 2 Diabetes due to insulin

resistance, growth hormone receptor defects