Lecture 3 Flashcards
1
Q
What is the major anterior pituitary hormone?
A
Growth hormone - ~10% dry weight
2
Q
What are the direct effects of growth hormone?
A
- Antagonises insulin (diabetogenic if there is long term production/release of GH) - Synergies with cortisol - Promotes growth –> bone, soft tissue and viscera –> Enhances fibroblast differentiation
3
Q
What are the indirect effects of growth hormone?
A
Via insulin-like growth factor (IGF-I), antagonised by cortisol
4
Q
Describe the feedback regulation involves in growth hormone (GH)
A
- Stimuli on hypothalamus
- Release of GH releasing hormone or GH inhibiting hormone (somatostatin) from hypothalamus
- Act on pituitary gland which releases GH –> Can be directly stimulated by thyroxine as well
- GH exerts negative feedback loop and has 2 major target structures –> Liver –> produces IGF-1 –> Adipose tissue –> another negative feedback loop
- Can be stimulation of growth hormone releasing hormone release through hyperglycaemia, or by a hormone released from stomach (Ghrelin)
5
Q
How does GH stimulate growth?
A
- Increased body protein content - Decreased body fat content
6
Q
What are the effects of GH on metabolism?
A
- Anti-insulin effects in muscle (decreased glucose uptake) –> Fat breakdown (stimulates lipolysis and inhibits lipogenesis) –> In excess, GH is diabetogenic
7
Q
What mediates the indirect effects of GH?
A
Mediated by somatomedins (IGF-I and IGF-II)
8
Q
What are the effects of GH on adipose tissue?
A
- Inhibits lipogenesis
- Stimulates lipolysis
- One exception = brown fat tissue –> Used to produce heat (not primarily used for energy) –> Increase in brown fat tissue with GH
- Inhibition of lipoprotein lipase (LPL)
- Stimulated hormone sensitive lipase (HSL)
- Decreased glucose transport into adipose tissue
9
Q
What are the effects of GH on liver?
A
- Gluconeogenesis in liver - IGF-1 is produced here too
10
Q
What are the effects of GH on muscle?
A
- Increase in muscle mass/muscle maintenance - Switch in fibres expressed - Muscle growth and released effects, e.g nitrogen retention - Increased AA transport into muscle - Increased nitrogen retention to increased muscle mass - Increased metabolically active tissue and increased energy expenditure
11
Q
What are the effects of GH on bones?
A
- Bone mineral density will increase - Mainly in legs - Increased activity of osteoclasts that break down bone - Increased osteoblast activity which make bone - Get turnover of bone and there is a favouring towards osteoblasts so bone mass increases
12
Q
What are the effects of IGF-1 on adipose tissue?
A
- Preadipocyte proliferation, differentiation and senescence (GH also involved)
13
Q
What are the key features of IGF-I? Where is it made, what does it do etc?
A
- Synthesised in liver - Polypeptide so cannot penetrate the cell membrane - Half life of GH is rather short (10-20 minutes) - IGF-I has a much longer half life (20 hours) - IGF-I drives differentiation of muscle cells –> GH can’t do this alone - IGF-I receptor is a dimer and has tyrosine kinase activity
14
Q
Through which pathway can GH have additional effects?
A
- GH also has some direct effects mediated by MAPK/ERK pathway - E.g chondrocyte amplification in cartilage
15
Q
What are the effects of GH on linear growth?
A
- Increased epiphyseal growth
- GH is believed to have double impact here –> Stimulates differentiation of pre-chondrocytes which contribute to maintaining process in epiphyseal areas –> Local production and expression of IGF-I here can lead to clonal expansion of osteoblasts so more bone formation
16
Q
What are the effects of GH on insulin?
A
- Not only involved in growth, also involved in maintaining blood glucose - Differential effects in the short term –> Acute effects that counters insulin action –> Increase insulin secretion from the pancreas - In long term (can be indirectly mediated), there will be a decrease in insulin signalling as there will be more IGF-1 in the body
17
Q
What are the symptoms of acromegaly?
A
- Change in appearance - Increased size of hands/feet - Headaches - Visual deterioration - Tiredness - Weight gain - Amenorrhoea - Impotence or poor libido - Deep voice - Goitre - Excessive sweating - Polyuria/polydipsia - Joint pains
18
Q
What are the causes of acromegaly?
A
- Caused by excessive GH secretion - This can be due to pituitary tumours
19
Q
What do the differences in acromegaly phenotypes depend on?
A
- Depend on when in life there is excessive GH secretion - Produce gigantism in children (before epiphyseal fusion)
20
Q
What effects do pituitary tumours have on vision?
A
- Tumours can only grow upwards and will compress the optic nerve - Causes visual dysfunction
21
Q
What can transgenic models be used for when considering acromegaly?
A
- Can make transgenic models (animal models) that have acromegaly - E.g mice that grow much larger - E.g salmon that have 11x the mass as normal - Interesting applications in food production
22
Q
Where are the adrenals located?
A
- Adrenals = situated on top of each kidney - Embedded in adipose tissue - Adrenals has a capsule with protective function just below the fat tissue
23
Q
What are the 4 different regions of the adrenal gland? What is produced in each place?
A
- Cortex: –> Zona glomerulosa –> Zona fasciculata –> Zona reticularis (on inner side of adrenal cortex) –> Different cells of cortex produce different steroids
- Medulla –> produces different hormones to the cortex –> Releases adrenaline and noradrenaline
24
Q
Where are hormones produced and stored in the adrenal gland? What are the advantages of this?
A
- Hormones are mainly produced in chromaffin cells –> These contain lots of storage granules –> They are situated very close to cholinergic nerve terminals –> Can have a direct CNS input to the adrenal medulla that causes the release of adrenaline/noradrenaline that is stored there
- Chromaffin cells are in close proximity to the blood vessels –> Anything released from them can quickly enter the circulation and exert immediate effects
25
What are catecholamines?
Hormones released from the adrenal glands
26
What are the effects of catecholamines?
- Responsible for flight or fight in immediate stress responses and adaptation to danger
- Heart rate and force is increased by adrenaline --> Increases blood pressure
- Lung tissue is relaxed (bronchodilation) to allow more air flow in
- Hyperglycaemia --> allows for a transient state of high glucose levels to provide higher energy levels for running away
- Free fatty acids in plasma (noradrenaline)
- Increased ACTH secretion in the anterior pituitary - Pupil dilation - Piloerection
27
What do mineralocorticoids do? Where are they typically produced?
- E.g aldosterone
- Not much effect ACTH on aldosterone synthesis/secretion
- Regulates Na+ and blood pressure (water homeostasis)
- Produced in outer part of cortex, called the zona glomerulosa
28
What do glucocorticoids do? Where are they typically produced?
- E.g cortisol - Glucose homeostasis - Plus many other effects - Typically produced in the middle part of cortex, called zona fasciculata
29
What do sex steroid precursors do? Where are they typically produced?
- Relatively minor - Final maturation of hormone in the gonads - Produced in the inner part of the cortex, called the zona reticularis
30
What is the precursor for mineralocorticoids, glucocorticoids and sex steroid precursors?
Cholesterol
31
What does ACTH stimulate and how does this affect the precursors of adrenal steroid hormones?
- ACTH has major role in stimulating 17 alpha hydroxylase (CYP17)
- Can shift precursor molecules from 1 area to another
32
What does the ACTH receptor do?
- Induces cAMP - Promotes steroidogenesis
33
What is the StAR protein? What does it do?
- Produced after ACTH receptor signalling
- Part of the mitochondria
- Can bring in cholesterol produced by LDL into mitochondria to allow downstream effects to happen
- Essential role in ACTH mechanisms
34
What are the effects of cortisol on bones?
- Decreases bone function - Increase bone resorption - Decreases connective tissue
35
What are the effects of cortisol on muscles?
- Maintains muscle function - Decreases muscle mass - Seems to counteract growth hormone
36
What are the effects of cortisol on cardiac output?
- Maintains cardiac output - Decreases endothelial permeability - Increases arteriolar tone --> can easily induce hypotension
37
What are some of the miscellaneous effects of cortisol around the body?
- Lots of function in emotional modulation
- Can get very tired if there's too much of it
- Increases productivity of the kidneys --> Produce more urine and have higher water clearance - Inhibits immune and inhibitory responses --> Can be used as an immunosuppressant
- Essential role in development of lungs in foetus --> Helps produce surfactant to help unfold lungs
38
What is POMC?
- POMC = pro-opiomelanocortin - POMC is very important --> Incredibly large --> Precursor of ACTH
39
Describe the different regions present within the POMC gene and what happens during processing
- Have at least 3 melanocyte stimulating hormone (MSH) released from POMC
- CLIP released from POMC --> Seems to have a role in sleep
- Beta-endorphin and met enkephalin are released POMC: --> Have anti-pain and euphoric effects --> Basis of 'runners high'
40
How can we disrupt the circadian regulation of cortisol secretion?
With stress
41
Give some examples of situations/events that lead to stress-induced cortisol secretion
- Physical trauma: --> Burns --> Fractures --> Infection
- Psychological stress: --> Exams --> Anxiety --> New situations
42
What is cortisol secretion a classic example of?
- Cortisol secretion is subject to classical negative feedback inhibition
- Can partially override with continuous stress
43
What are the effects of glucocorticoids on carbohydrate metabolism?
- Promotes gluconeogenesis - Decreased use of glucose - Elevated blood glucose --> diabetogenic
44
What are the effects of glucocorticoids on protein metabolism?
- Reduction in cellular protein - Increased blood amino acids
45
What are the effects of glucocorticoids on fat metabolism?
- Mobilisation of fatty acids
46
How do glucocorticoids exhibit feedback repression on the HPA axis?
- Repress release and activity of CRH, ACTH etc
47
Give some examples of adrenal diseases caused by the overproduction of glucocorticoids
- Cushing's disease
- High blood pressure
- Immune suppression
48
Give an example of an adrenal disease caused by insufficient production of cortex steroids
- Addison's disease --> Caused by lack of aldosterone --> Also called hypoadrenalism
49
What are the symptoms of Cushing's disease?
- Central weight gain - Change in appearance - Depression - Psychosis - Insomnia - Amenorrhoea - Poor libido - Thin skin - Bruising - Growth arrest - Back pain - Polyuria/polydipsia
50
What are the causes of over-production adrenal diseases?
- ACTH-Dependent causes: --> Pituitary-dependent (Cushing's) --> Ectopic ACTH-tumour --> ACTH administration
- Non-ACTH-Dependent causes: --> Adrenal adenomas and carcinomas
51
What are the symptoms of Addison's disease?
- Postural hypotension - Weight loss - Anorexia - Weakness - Fever - Depression - Impotence/amenorrhoea - Nausea/vomiting - Diarrhoea/constipation - Confusion - Abdominal pain - Back pain
- Bronzing of skin: --> ACTH production will increase --> Need more POMC to get more ACTH so also produces more melanocyte stimulating hormones so causes tan
52
What are the causes of Addison's disease? Include what happens to the adrenal cortex
- Autoimmune disease (90% in UK) - Tuberculosis (10% in UK) - Destruction of adrenal cortex - Reduced glucocorticoid, mineralocorticoids and sex steroid production - Lack of aldosterone
