Endocrine Flashcards
Name the two main hormones stored in the posterior pituitary gland.
Oxytocin and vasopressin (ADH)
Describe an example of direct cell signalling
Movement of ions from cell to cell through a gap junction
Compare paracrine and autocrine signalling
Paracrine - signalling molecule is released from one cell and acts on a neighbouring cell
Autocrine - signalling molecule released from a cell and binds to a receptor on the same cell
Define neurohormone
A hormone produced in a neuron
Which class of hormones are derived from the amino acid tyrosine? List some examples
Catecholamines
Examples= adrenaline, noradrenaline, dopamine
Steroid hormones a sub-section of which class of hormones?
Lipid derived
Eicosanoid hormones are lipid derivatives of……
Arachidonic acid
Steroids are structurally related to….
Cholesterol
Lipid hormones are only 1% biologically active because they form complexes with…
Plasma proteins
Polypeptide hormones commonly need to be ….. before they become biologically active
Metabolised
When a hormone binds to a receptor, the 3 ways this initiates a physiological response are:
- Alters channel permeability by acting on the proteins forming the channel in the cell membrane
- Acts through a second messenger system
- Activates specific genes to cause the formation of new proteins
(Can be one, two or all of these)
Insulin binds to which type of receptor?
Tyrosine kinase receptor
Which hormone receptor type is located intracellularly and why?
Steroid receptors.
This is because steroid hormones are lipid derived and can easily cross the membrane
How does molecular recognition decrease the physiological response following a hormone release?
Molecular recognition = decreased or no target receptors present.
Compare type 1 and type 2 diabetes
Type 1 = insulin deficiency
Type 2 = signal transduction is altered by other hormones which limits the efficacy of insulin
Decreased hormonal activity could be caused by (name at least 3)
Hyposecretion, increased removal of hormone from the blood stream, lack of target receptors, abnormal tissue responsiveness
Reduced formation of plasma protein - hormone complexes would result in…
Increased concentration of the free, biologically active compound, leading to increased hormonal activity
Decreased inactivation or excretion and decreased removal of the hormone from the bloodstream could cause…
Increased hormonal activity
What is the hypothalamus made up of
Nuclei (neuronal cell bodies) and axons
Which nuclei in the hypothalamus produce oxytocin and vasopressin
Paraventricular nucleus
Supraoptic nucleus
Oxytocin and vasopressin are both…
Short peptide chains (~9 amino acids in length)
The secretion / release of a neurohormone requires…
A change in electrical activity (action potential)
What differences would be visually present when comparing the anterior and posterior pituitary glands?
The anterior would be darker (more staining due to the dye) because it contains more cell bodies, whereas the posterior would be lighter since it mainly contains nerve terminals and capillaries
Which factors regulate ADH release from the posterior pituitary gland?
Solute concentration and blood volume
What factors regulate oxytocin release?
Pressure of the baby in the birth canal, suckling on the nipple
Note= secretion is inhibited by fear and anxiety
Oxytocin can also be released in response to sensory stimuli such as ….
Seeing and hearing the baby (auditory and optic input)
Briefly describe the milk ejection reflex
The baby suckling creates a signal which synapses in the dorsal horn of the spinal cord, then travels to the paraventricular and supraoptic nuclei. The action potential travels down the axon to the posterior pituitary gland, initiating the secretion of oxytocin into the bloodstream
The area of the hypothalamus where the BBB is not completely formed is called…
Median Eminence
Output and input to/from the hypothalamus can be either neural or humoral. Explain each.
Neural = signal travels to/from the hypothalamus to/from other areas of the brain
Humoral = hypothalamus releases hormones as a result of a stimulus detected in the blood or CSF
Provide an example of a humoral stimulus
Low blood glucose levels triggers the pancreatic release of insulin
Effect of oestrogen on oxytocin?
High levels of oestrogen (during labour and pregnancy) up-regulates oxytocin mRNA production
What is the target cell of oxytocin in the breast?
The myoepithelial cells. This is the smooth muscle surrounding the secretory alveolar. It promotes the ejection of milk down the ducts.
Explain how oxytocin binding to the myoepithelial cell initiates a physiological response.
Oxytocin binds to the GPCR. The second messenger acts through PLC which splits into DAG and IP3. The IP3 binds to the SR or ER. This promotes the release of calcium into the lumen, which binds to troponin, causing actin and myosin crossbridges to form.
What is the oxytocin nasal spray used for?
Increases milk let down
What does a continuous IV infusion of oxytocin do?
Increases contractile force during labour. This also prevents post-labour haemorrhage
What are oxytocics?
Synthetic oxytocin’s
What is atosiban?
An oxytocin analog / competitive antagonist. Used to prevent / delay pre-term labour
What is a somatotroph
Cell in anterior pituitary that produces growth hormone (GH)
What hormone does lactotroph produce
Prolactin
Which hormones do gonadotrophs produce?
Luteinising hormone (LH) and Follicle Stimulating Hormone (FSH)
Which hormone does tyrotroph cells produce?
Thyroid stimulating hormone (TSH)
Which hormone does corticotroph cells produce?
Adrenocorticotrophic hormone ACTH
Which two hormones produced in the anterior pituitary have a direct physiological effect rather than acting on another endocrine gland?
Prolactin and growth hormone
How are releasing factors / hormones sent to the anterior pituitary from the hypothalamus?
They are secreted from nerves into capillaries at the median eminence region of the hypothalamus. They are sent to the anterior pituitary through the blood connection
Releasing factors are short peptides (3-40 amino acids). Why is it important that they are short
Once released from hypothalamus, they only need to have a very short duration of action. Once they have their effect on the anterior pituitary, they are rapidly metabolised in systemic circulation
What evidence is there that prolactin is controlled by an inhibiting factor rather than releasing?
Hypothalamo-pituitary disconnection. When the connection is severed, prolactin levels go up, whereas the other hormones are decreased.
Growth hormone release is inhibited by…
Somatostatin
What is the long term effect of dopamine on lactotrophs?
Dopamine inhibits the proliferation of lactotrophs
Which receptor on the lactotroph does dopamine bind to?
D2
How is prolactin secreted from lactotroph?
AP arrives at lactotroph, opening voltage gated calcium channels. This initiates a cascade of events leading to the exocytosis of prolactin
Explain the use of haloperidol.
D2 antagonist = stimulates prolactin
Bromocriptine (used to treat prolactinoma and hypersecretion) is a….
Dopamine agonist
What effect does oestrogen have on prolactin?
Up regulates the synthesis of prolactin
E.g. during pregnancy
Where does prolactin bind within the body?
Aveolar epithelial cells of mammary gland
Stimulates the cell to synthesise and secrete milk
How long is GH?
191 amino acids
GH inhibiting factor?
Somatostatin
GH release / concentration is…
Pulsatile
During which stage of sleep is GH released?
Non-REM, a few hours into sleep (around midnight)
What is the difference between males and females GH concentrations?
GHRH release in females is more continuous than in males. The peaks are smaller in size but more frequent
What is the hypothalamic-hypophyseal portal system?
The blood vessel network connecting the hypothalamus to the pituitary
Why is GH release pulsatile?
Because of the alternating release of GHRH and somatostatin
How does somatostatin inhibit GH release?
When it binds to somatotroph, somatostatin activates an inhibitory G protein which prevents the exocytosis of GH
Describe the negative feedback loop of GH
Once released into blood stream, GH re-enters the CSF and feeds back to the hypothalamus. This switches off release of GHRH and turns on release of somatostatin.
Define hyperplasia
Increase in the number of cells
Define hypertrophy
Increase in the size of cells
What effect does GH have on bones?
Increases the thickness and length
Main signalling pathway of prolactin and growth hormone?
JAK/STAT
Describe somatomedin hypothesis
GH binds to hepatocytes, which causes the release of IGF1, which is responsible for the physiological actions. Idea is that GH itself doesn’t cause actions, but rather a secondary hormone.
What does IGF1 stand for?
Insulin-like growth factor 1
IGF1 and GH both use which signalling pathway?
MAPKinase
Where is IGF1 produced?
In the liver
Where are GH receptors found
In most tissues
When in life are the two biggest growth spurts seem?
Early childhood and pubertal
Where in the bone does cell division occur
At the growth plate
Which hormone controls cell hypertrophy?
IGF1
What causes the closure of the growth plates after puberty?
Oestrogen
How does GH /IGF1 affect bones after growth plate closure?
Can only increase the thickness
What is the epiphyses?
The region of bone where growth occurs
Does GH increase or decrease blood glucose? MOA?
Increase. GH inhibits glucose reuptake
GH increases lipolysis. Define this.
Lipolysis = fat breakdown
Define gluconeogenesis
The production of new glucose
Role of GH in starvation?
Increases gluconeogenesis in the liver. (Liver produces more glucose)
A deficiency in thyroid hormones causes what issue in growth?
Stunted growth
How does cortisol effect growth?
Too much cortisol inhibits growth by breaking down proteins
How does untreated insulin deficiency alter growth?
Causes abnormal growth
Is IGF1 involved in the metabolic processes of GH?
No
How does GHRH increase GH?
It increases gene expression in somatotroph
Why does pulsatility of GH decrease after puberty?
Because of decrease in sex hormones
Which 3 metabolic stimuli (received by the hypothalamus) can increase GH release?
- high amino acid concentration
- low fatty acid concentration
- hypoglycaemia (low blood glucose)
Define acromegaly
Hypersecretion of GH in adulthood (likely pituitary tumour)
Why does hyper/hypo secretion of GH affect children’s stature but not adults?
Because their growth plates are still open
Acromegaly causes which major symptoms?
Thickening of the bones in the feet, hands and face
Thickening of soft tissue (particularly facial features)
Why is recombinant hGH expensive?
Because it is a longer peptide and therefore harder to synthesise
Explain use of octreotride
Somatostatin agonist - inhibits excess GH in acromegaly and gigantism
Compare somatropin and mecasermin
Somatropin = recombinant hGH
Mecasermin = recombinant IGF 1
Both used for growth defects
Which medication is sometimes ineffective in children and has to be replaced with mecasermin
Somatropin
Name a somatostatin agonist
Octreotride
