What is a hormone?
Blood‐borne chemical mediator released from endocrine glands that act on distant target cells
What is the difference in the type of chemical messenger used between the nervous system compared to the endocrine system?
Neurotransmitters are released into the synaptic cleft. Hormones are released into the blood.
What is the difference in the distance of action between the nervous system compared to the endocrine system?
NS: Very short distances into synaptic cleft
ES: Long distance (carried by blood)
What is the difference in the means of specificity of action on the target cell between the nervous system compared to the endocrine system?
NS: Dependent on close anatomic relationship between nerve cells and their target cells. ES: Dependent on specificity of target cell binding and responsiveness to a particular hormone.
What is the difference in the speed of response between the nervous system compared to the endocrine system?
NS: Rapid (milliseconds) ES: Slow (minutes to hours)
What is the difference in the duration of action between the nervous system compared to the endocrine system?
NS: Brief (milliseconds) ES: Long (minutes to days or longer)
What is the difference in the major functions between the nervous system compared to the endocrine system?
NS: Coordinates rapid, precise responses
ES: Controls activities that require long duration rather than speed.
Can endocrine glands produce multiple hormones?
Yes - E.g. pituitary gland
Can hormones be produced by multiple endocrine glands?
Yes - E.g. sex steroids.
Can hormones have more than one target and function?
Yes - E.g. sex steroids; GH
In what type of a pattern does the rate of secretion of some hormones vary?
Over time, in a cyclic fashion - E.g. sex steroids.
Can a single cell/organ be influenced by more than one hormone?
Yes - E.g. pancreas; reproductive system.
Can the same chemical messenger be a hormone and a neurotransmitter?
Yes - E.g. noradrenaline.
What are autocrine signals?
Chemical messengers acting on the same cell that secreted them.
What are paracrine signals?
Chemical messengers that are secreted by one cell and diffuse to adjacent cells. Used for local communication.
What cells will respond to hormonal signals?
Those with receptors for the hormone.
What are neurotransmitters?
Chemicals secreted by neurons that diffuse across a small gap to the target cell. Neurons use electrical signals as well.
What are neurohormones?
Chemicals (neurocrines) released by neurons into the blood for action at distant targets.
What are the 3 major groups of neurohormones and where do they originate from?
Hypothalamus → anterior pituitary
Hypothalamus → posterior pituitary
Catecholamines (made by modified adrenal medulla neurons).
What is a tropic hormone?
A hormone that controls the secretion of another hormone
What is a trophic hormone?
A hormone that stimulates growth and development.
What are some examples of tropic hormones?
Thyrotropin (TSH), Corticotropin, ACTH
What does the neurohormone reflex entail?
A stimulus acting at a neuron, which then stimulates a neuroendocrine cell in the CNS to release neurohormones into the circulation which then act at a distant receptor.
What comprises the simple endocrine reflex?
Stimulus acts on endocrine integrating centre, which then releases a hormone into the blood stream to act on a receptor in the target cell (effector)
What are the different schemes of hormone classification?
Structure e.g. Peptides, Amines, Steroids
Solubility e.g. hydrophilic or lipophilic
Binding of Receptor Type e.g. G protein‐coupled receptors, tyrosine kinase‐linked receptors, etc.
When are peptides synthesised and where are they stored?
Made in advance; stored in secretory vesicles.
When are steroid hormones synthesised?
Synthesised on demand
When are catecholamines synthesised and where are they stored?
Made in advance; stored in secretory vesicles
When are thyroid hormones synthesised and where are they stored?
Made in advance; precursor stored in secretory vesicles.
How are hydrophilic/lipophobic hormones released from the parent cell?
How are hydrophobic/lipophilic hormones released from the parent cell?
If a protein is hydrophilic/lipophobic, how will it be transported in the blood?
Dissolved in plasma
If a protein is hydrophobic/lipophilic, how will it be transported in the blood?
Bound to carrier proteins
Which classes of hormones are hydrophilic/lipophobic?
Peptide hormones and catecholamines
Which classes of hormones are hydrophobic/lipophilic?
Steroid hormones and thyroid hormones
Where will the cell receptor for hydrophilic/lipophobic hormones be located?
Where will the cell receptor for hydrophobic/lipophilic hormones be located?
In the cytoplasm or nucleus; some have membrane receptors also.
What is the receptor response to hydrophilic/lipophobic hormone ligand binding?
Activation of second messenger systems; may activate genes (e.g. peptide hormones)
What is the receptor response to hydrophobic/lipophilic hormone ligand binding?
Activation of genes for transcription and translation; may have non-genomic actions (e.g. steroid hormones).
What is the general target response to hydrophilic/lipophobic hormones?
Modification of existing proteins (and induction of new protein synthesis if a peptide hormone)
What is the general target response to hydrophobic/lipophilic hormones?
Induction of new protein synthesis.
What are some examples of peptide hormones?
Insulin, parathyroid hormone
What are some examples of steroid hormones?
Oestrogen, androgens and cortisol
What are some examples of catecholamines?
What are some examples of thyroid hormones?
How are peptide hormones synthesised?
mRNA on the ribosomes binds amino acids into a peptide chain preprohormone, which is then directed into ER lumen.
Enzymes in ER chop off signal sequence, creating inactive prohormone
Prohormone passes from ER through the Golgi complex
Secretor vesicles containing enzymes and prohormone bud off from Golgi complex.
Enzymes chop prohormone into active peptide(s) plus additional peptide fragments
Secretory vesicles release contents by exocytosis into EC space
Hormone moves into circulation for transport to target cell
How are steroid hormones synthesised?
Cholesterol parent compound is modified by enzymes to make steroid hormones such as aldosterone or cortisol in the adrenal cortex or oestradiol in the ovary.
How are the amine hormones synthesised?
Tyrosine is convered into catecholamines (dopamine, adrenaline or noradrenaline) or thyroid hormones (T4 or T3)
What is the mechanism of action of peptides and catecholamines?
Peptide hormones cannot enter their target cells and must combine with membrane receptors that initiate signal transduction processes via second messenger systems using tyrosine kinase of amplifier enzymes.
Why can't peptides and catecholamines enter their target cells?
Because they are hydrophilic/lipophobic, meaning they must act at membrane receptors, initiating second messenger systems.
What are most hydrophobic steroids bound to?
Plasma protein carriers
What is the mechanism of action of steroid hormones?
Unbound steroid hormone diffuses into target cell, binds to receptors in cytoplasm or nucleus, receptor-hormone complex binds to DNA and activates or represses gene(s). New mRNA created that moves back to cytoplasm to be translated, producing new proteins.
What do steroid hormones alter?
Gene expression and production of new proteins
What do thyroid hormones behave like?
What does plasma concentration of free, biologically active hormone depend on?
1. Hormone's rate of secretion by endocrine gland (major factor for all hormones) 2. Rate of metabolic activation (for a few hormones) 3. Extend of binding to plasma proteins (lipophilic hormones) 4. Rate of metabolic inactivation and excretion (all hormones)
What must a hormone be to be active?
Where are hormones removed?
Liver → Kidney → Urine
How are steroid hormones removed?
Through conjugation and then via the urine and bile.
How are amine hormones removed?
By specific circulating degrading enzymes.
How are large peptide hormones removed?
By receptor-mediated endocytosis
How are most smaller peptide hormones removed?
By the kidneys
How is hormone secretion regulated?
By positive and negative feedback loops.
What are the two different types of negative feedback regulation of hormone secretion?
Long and short loops.
Which of the feedback loops is a back-up?
What is short-loop negative feedback?
Trophic hormone (H2) inhibits hypothalamus (IC1)
What is long-loop negative feedback?
Hormone (H3) inhibits hypothalamus (IC1)
What is an example of positive feedback control of hormone secretion?
Luteinizing hormone provides positive feedback for more hormone release, resulting in an LH surge and dilation of the cervix during labor.
Which two structures and their hormones are regulated by diurnal and circardian rhythms?
Pineal Gland: Melatonin (hormone of darkness)
Suprachiasmatic Nucleus: Accumulation of clock proteins
What are the 4 different ways in which hormone activity can be regulated?
Down‐regulation - Endocytosis, Target cell desensitisation
Antagonism - Act together but act in opposite directions (insulin & glucagon), Allows fine tuning
Synergism - Multiple stimuli and effect is more than additive (glucagon, cortisol & adrenaline regulating blood glucose; reproductive)
Permissive - First hormone cannot exert effects without presence of second hormone (cortisol & adrenaline)
What are the 3 possible causes of decreased hormone activity?
Increased removal from blood
Abnormal tissue response
What are the 2 different types of hyposecretion?
Primary (gland abnormal)
Secondary (normal gland; abnormal tropic hormone)
What are the 2 possible reasons for abnormal tissue response to a hormone?
Lack of receptors or enzyme for cell response.
What is the treatment for decreased hormone activity?
What are the 3 possible causes of increased hormone activity?
2. Decreased plasma protein binding
3. Removal from blood
What are the 2 different types of hypersecretion?
Primary (gland abnormal) and secondary (normal gland; excessive stimulation)
What could be the cause of decreased removal of hormone from the blood?
Decreased inactivation or excretion.
What is the treatment for increased hormone activity?
Tumour removal or inhibiting drugs
What will happen to hormone levels in a secondary hypersecretion problem when pathology is in the hypothalamus?
CRH, ACTH and Cortisol levels will increase.
What will happen to hormone levels in a secondary hypersecretion problem when pathology is in the pituitary?
CRH levels will decrease, ACTH and cortisol levels high.
What will happen to hormone levels in a primary hypersecretion problem when pathology is in the adrenal cortex?
CRH and ACTH levels low, cortisol levels high.