Module 5 summary: Endorinology

Water soluble hormone pathway:

1. Travel freely in bloodstream

2. Act on receptors on plasma membrane
3. Signalling transduction pathway
4. Causes cytoplasmic response or some alteration to gene transcription

Lipid Soluble hormone pathway:

1. Bind to transport proteins to keep them soluble in blood

2. Unbind transport proteins and diffuse into target cell
3. Binds to receptors inside the cytoplasm or nucleus
4. Intracellular receptors transduce signal inside the cell
5. Directly results in changes in gene transcription

Adrenaline pathway (water soluble):

1. Adrenal glands secrete hormone adrenaline in response to stress

2. Adrenaline binds to GPCR in plasma membrane of target cells in liver
3. Binding of hormone triggers cascade of events which leads to synthesis of cAMP
4. cAMP activates protein kinase A in order to:
a. Activation of enzyme which breakdown glycogen
b. Inactivation of enzymes which synthesise glucose
5. The effect is that liver releases glucose into the blood stream for burst of energy

Oestradiol Pathway (lipid soluble):

1. Oestradiol binds to receptors in cytoplasm

2. Hormone receptor complex moves to nucleus and acts as a transcription factor to promote
transcription of Vitellogenin gene (precursor protein of egg yolk)

How can Adrenaline cause multiple outcomes?

- Different receptors have different functions

o Beta receptors in skeletal muscle -vasodilation
o Alpha receptors in intestines - vasoconstriction
o Beta receptors in liver cells glycogen breakdown
- Different intracellular protein

Example of negative feedback: thyroid hormone cascade

Stimulus: body temperature drops below normal levels

1. Hypothalamus detects
2. Hypothalamus secrete TRH into blood
3. TRH binds to target cells in anterior pituitary gland
4. Anterior pituitary gland secretes TSH

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 5. TSH binds to thyroid gland to produce thyroid hormones
6. Hormones increase metabolism
7. Negative feedback: thyroid hormones inhibit TRH and TSH

Example of Positive feedback:

Stimulus: baby drinking milk from mothers breast

1. Detection via hypothalamus

2. Posterior pituitary secretes oxytocin into blood
3. Oxytocin acts on smooth muscle in breasts causing milk ejection
4. Positive feedback is when stimulus is reinforced by the baby sucking more as more milk is
ejected.

Homeostasis achieved by antagonistic pairs or hormones (opposing effects):

When blood glucose levels are high:

1. Insulin is produced in Beta pancreas cells

2. Insulin promotes storage of glucose as glycogen in liver
3. Also promotes cells to take up glucose
4. Glucose levels decline in blood

When blood glucose levels are low:

1. Glucagon produced in alpha pancreas cells

2. Glucagon breaks down glycogen into glucose in liver causing release of glucose
3. Glucose levels rise in blood

Homeostasis when blood pressure is low (RAAS)

1. Blood pressure detected by JGA in hypothalamus

2. JGA secretes renin enzyme
3. Renin converts angiotensinogen to angiotensin I
4. ACE converts angiotensin I to angiotensin II
5. Angiotensin II acts:
a. On adrenal gland causing release of aldosterone increases Na+ uptake and water
uptake in kidney
b. Constriction in arterioles
6. Increases blood pressure

Homeostasis when blood osmolarity is high (>300mOsm/L)

1. Osmoreceptors in hypothalamus trigger feelings of thirst and release anti-diuretic hormone

(ADH) vasopressin.
2. Vasopressin acts on distal tubules and collecting ducts in kidneys
a. Makes epithelium more permeable to water
3. This increases renal reabsorption of water and reduces urine volume
4. Negative feedback occurs to prevent production of vasopressin

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 Adrenal gland

Composed of two glands:

Adrenal cortex - Endocrine gland - made up of actual endocrine cells

- Releases corticosteroids (class steroid hormones), two main types:
- Mineralocorticoids mediate mineral metabolism (salt/water)
balance (e.g. aldosterone)
- Glucocorticoids mediate glucose metabolism (e.g. cortisol)

Adrenal medulla - Neuroendocrine gland secretory cells actually neural tissue

- Rapid response to short term stress - trigger fight-or-flight
response
- In stress response releases catecholamines (class of amine
hormones):
- Epinephrine (Adrenaline)
- Norepinephrine (Noradrenaline)

Hypothalamus and pituitary hormones

Hypothalamus plays significant role in endocrine signalling

- Sensory information passed to hypothalamus

- Hypothalamus signals pituitary gland to secrete hormones

Posterior Pituitary Anterior Pituitary

Extension of hypothalamus Endocrine gland that synthesizes and secretes
Neurohormones synthesized in the hypothalamus hormones in response to hormones from the
then travel down axons where they are stored in hypothalamus
the Posterior Pituitary Neurosecretory cells in hypothalamus secrete
Hypothalamus triggers Posterior Pituitary to hormones into capillary bed at base of
release Neurohormone into blood at appropriate hypothalamus (called tropic hormones since they
time via nerve impulses control other endocrine cells)
Does not synthesize hormones itself, only store capillaries drain into portal vessels which then
and release subdivide into second capillary bed within anterior
Secretes: ADH & Oxytocin pituitary
Both polypeptide hormones Hormones from the hypothalamus then mediate
ADH acts on kidney tubules the release of anterior pituitary hormones (from
Oxytocin acts on mammary glands and uterine highly diversified endocrine cells within anterior
muscles (eject milk & birth baby) pituitary)

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Module 3 Skeletal muscle

Muscle contraction:

1. Acetylcholine (Ach) is released from synaptic terminal of motor neuron

2. Ach binds to nicotine receptors, allowing Na channels to open Na+ comes into the cell
3. This results in an action potential which gets propagated along the muscle surface resulting
in depolarisation event
4. Action potential triggers release of Ca2+ from sarcoplasmic reticulum
5. Ca2+ binds to tropomysin and changes it shape to expose myosin binding sites
6. ATP bound to myosin head is hydrolysed which moves myosin to a high energy state, causing
a cross bridge to be formed with actin
7. Release of ADP+phosphate returns myosin to low energy state
8. Low energy state pulls actin toward the myosin head and by extension toward the centre of
sarcomere (power stroke)
9. Binding of new molecule of ATP releases myosin head from actin, and a new cycle begins

Muscle fibre twitches are all or nothing responses: when contracts, it contracts completely not a
graded response

- Ability to generate tension is dependent on sarcomere length

- Too much extension
o Myosin and actin do not overlap significantly enough for power strokes to exert
significant force
- Too much compression
o Actin interfere destructively across M line

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Module 4:

Determinants of blood pressure

- Mainly cardiac output

- Nervous and endocrine system
o Affect contraction of smooth muscles in arterioles
o Vasoconstriction smooth muscle contracts arterioles narrow BP increase
o Vasodilation smooth muscle relax arterioles expand BP decrease
o Allows for regional regulation of BP

Regeneration of erythrocytes (RBC)

- Kidney detects low O2 carrying capacity in blood

- Kidney releases hormone enthropoietin
- Enthropoietin acts on bone marrow stimulating production of enthrocytes from myeloid
stem cells
- Oxygen carrying capacity increased
- Once oxygen carrying capacity is increased back to set point, kidney stops releasing
enthropoietin, stopping RBC production
- Homeostasis regained

Blood clotting:

1. Damaged blood vessel exposes collagen on endothelial layer

2. Platelets adhere to collagen and secrete sticky substances that allow other platelets to stick
forming a platelet plug
3. Platelets activate clotting factors resulting in clotting cascade
4. Inactive prothrombin gets converted to active thrombin
5. Thrombin then converts inactive fibrinogen to fibrin
6. Fibrin aggregates into threads that form a framework of fibrin clot

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Regulation of breathing in humans

Stimulus: when CO2 levels rise, reaction proceeds resulting in blood pH being lowered (<7.4)

1. Medulla detects pH decreased by two mechanisms

a. Medulla detects decreased pH in the cerebrospinal fluid which surrounds it
b. Chemoreceptors in major blood vessels detect decrease in blood pH -> relay
information to medulla
2. Medulla activates response leading to increased rate and depth of respiration
3. CO2 levels return to normal
4. Negative feedback regulates rate and depth of breathing back to neutral

pH dependence Bohrs Shift

- Haemoglobin retains less O2 at lower pH

- When CO2 level rises, reaction proceeds resulting in blood pH being lowered (e.g. during
exercise)
- Low pH reduces affinity of haemoglobin for O2

Positive cooperativity

- The more O2 attached to the haemoglobin the easier it is for next molecule to attach
- Conversely, when four O2 are bound, and one O2 is unloaded, the other 3 are more readily
unloaded
- Due to positive cooperativity, relatively small shift in bodily issue pO2 results in a large
amount of O2 being released from haemoglobin
o E.g. during exercise pO2 drops in muscle cells, however positive cooperation results
in large increase of blood O2 being supplied to the muscle.