Flashcards in Metabolism S9 - Disorders of Adrenal and Pituitary Glands Deck (34):
List the hormones produced in the Anterior pituitary gland and include the cell type that produces them.
TSH - Thyrothrophs
ACTH - Corticotrophs
Growth Hormone - Somatotrophs
LH and FSH - Gonadotrophs
Prolactin - Lactotrophs
What are the three zones of the adrenal cortex?
List them from Apical descending
Also, give the type of hormone secreted from each layer, along with an example of a hormone of that type.
E.g. Aldosterone (C21)
E.g. Cortisol, Corticosterone (C21)
E.g. Testosterone (C19)
What is produced in the Medulla of the Adrenal Gland?
Describe in detail how ACTH stimulates synthesis of Cortisol.
ACTH is hydrophilic and so binds to cell surface receptors in the zona fasciculata and reticularis.
Receptors are melanocortin type 2 receptors (aka Corticotrophin receptors)
This receptor uses cAMP as a secondary messenger
This leads to activation of cholesterol esterase increasing conversion of cholesterol esters to free cholesterol
Cortisol production from free cholesterol is therefore increased.
It also stimulates other steps in the synthesis of Cortisol from Cholesterol
What are the metabolic effects of Cortisol?
Relate this to location where applicable.
Decreased Amino acid uptake and protein synthesis
Increased Gluconeogenesis and glycogenolysis in liver
Increased lipolysis in adipose tissues
(High levels of cortisol increase Lipogenesis in adipose tissue)
What effects does cortisol have that aren't metabolic?
Direct effects on cardiac muscle, bone and the immune system
Describe the effects of aldosterone on the body.
What are the effects of over or undersecretion?
Stimulates Na+ reabsorption in the kidney in exchange for K+ or H+
Oversecretion increased Na+ and water retention and increases loss of K+ causing hypertension and muscle weakness
Undersecretion does the opposite, causing hypotension
What is the effect of androgens on the body?
What is the effect of oversecretion of androgens in a female?
Stimulate growth and development of male genital tract and male secondary characteristics.
Eg. Height, Voice deepening, Body shape, Facial and body hair and anabolic effects on muscle proteins
In females, oversecretion leads to:
Hair growth, acne, menstrual problems, increased muscle bulk and deepening voice
Describe the effects of Oestrogen on the body
Stimulate development of female genital tract, breast and secondary female characteristics such as:
Broad hips, accumulation of fat in breasts and buttocks, body hair distribution
They are weakly anabolic and decrease circulating cholesterol levels
Describe the structure of Cortisol.
How do C21 steroids differ from other steroids?
Number of C atoms
Presence of functional groups
Distribution of C=C double bonds
How are steroids transported around the body?
They are lipophilic therefore must be transported bound to plasma proteins
(90% transcortin - 10% free and active)
How are steroids synthesised in the body?
Synthesised from cholesterol via progesterone in a series of enzyme catalysed reactions
Describe the mechanism of action of cortisol upon its target cells
Cortisol crosses the plasma membrane as it is lipophilic
Binds to cytoplasmic receptors
The hormone receptor complex then enters the nucleus to interact with specific regions of DNA
This interaction changes rates of transcription of specific genes
The effect may therefore take some time to manifest.
Describe the mechanism of action of Adrenaline upon its target cells
Adrenaline is hydrophilic and so doesn't cross the plasma membrane
Instead it binds to adrenoreceptors on the cell surface
A secondary messenger then affects cell activity
How is cortisol secretion controlled?
What type of control does cortisol itself exert on the brain?
Through the HPA axis
Hypothalamus releases Corticotrophin releasing hormone
Which stimulates the Anterior Pituitary to release ACTH
Which in turn stimulates release of Cortisol
Cortisol exerts negative feedback control on both the Hypothalamus and the Anterior Pituitary
What is Corticotrophin releasing hormone released in response to?
Hint: Think about what CRH release leads to
Physical stressors (temperature, pain)
Chemical stressors (hypoglycaemia)
How are catecholamines synthesised?
Where are catecholamines stored?
Series of enzyme catalysed steps that convert:
Tyrosine to Dopa
Dopa to Dopamine
Dopamine to Noradrenaline
Noradrenaline to Adrenaline (via methylation)
Stored in the adrenal medullary cells in vesicles
Why is adrenaline released and what effects does it have on the body?
Released as part of the fight/flight/fright response in response to stress situations
Its effect include:
Increased cardiac output and blood supply to muscle
Increased mental alertness
Increased Glycogenolysis in liver and muscle
Increased lipolysis in adipose tissue
What are the clinical consequences of oversecretion of adrenaline?
Why might this overproduction occur?
Overproduction normally a result of tumour (Phaemochromocytoma)
What peptides can be derived from POMC?
Post translational processing of POMC produces different biologically active peptides such as:
How does ACTH lead to increased pigmentation in certain areas of the body?
ACTH's primary sequence contains the alpha-MSH sequence.
This gives ACTH some alpha-MSH like activity when present in excess.
What are the possible causes of Cushing's syndrome?
Adrenal cortex tumour (adenoma)
Ectopic ACTH secretion
Both result in excess secretion of cortisol/glucocorticoids
What are the clinical effects of excess cortisol secretion?
Increased muscle proteolysis and hepatic gluconeogenesis that can lead to hyperglycaemia, polyuria and polydipsia (Steroid Diabetes)
Wasting of muscles of the limbs
Increased lipogenesis in adipose
Deposition of fat in the abdomen neck and face (Moon shape face, dorso-cervical fat pad and central weight gain)
Purple striae on lower abdomen, upper arms and thighs reflecting proteolysis of proteins in the skin.
Easy bruising results from proteolysis and lipolysis in skin and subcutaneous tissue.
Immunosupressive, anti-inflammatory and anti-allergenic reactions leading to increased susceptibility to bacterial infections and producing acne
May be back pain and collapse of ribs due to osteoporosis caused by disturbance of Ca2+ metabolism and loss of bone matrix proteins
Mineralocorticoid effects of cortisol may produce hypertension due to Na+ and fluid retention
What may be the cause of Addison's disease?
Diseases of the adrenal cortex (auto-immune destruction) reduce glucocorticoids and mineralocorticoids
Disorders of the pituitary or hypothalamus lead to decreased secretion of ACTH or CRH - only affecting glucocorticoids
Both of these have the effect of lowering levels of cortisol secretion.
What are the clinical effects of too little cortisol secretion as a consequence of autoimmune destruction of the adrenal medulla?
Insidious onset with initial non-specific symptoms such as:
Tiredness, extreme muscular weakness, anorexia, vague abdominal pain, weight loss, occasional dizziness and dehydration
More specific sign is increased pigmentation due to increased ACTH secretion (due to lack of negative feedback from cortisol)
Decreased blood pressure due to Na+ and fluid depletion
Hypoglycaemia (esp. on fasting) due to decreased catabolism
What factors may exacerbate Addison's disease and what might this exacerbation lead to?
Stress, trauma or severe infection can lead to the development of an Addisonian crisis.
Symptoms of this include:
Nausea, vomiting, extreme dehydration, hypotension, confusion, fever and even coma.
How must an Addisonian crisis be treated?
Must be treated immediately with IV cortisol and fluid replacement (dextrose in saline) to avoid death.
What are the 3 tests for adrenal cortical function?
Measurement of ACTH/Cortisol levels
Dexamethasone Suppression test
How is an ACTH/Cortisol level test carried out?
Measurement of cortisol/ACTH directly in plasma
24hr cortisol and cortisol breakdown products (17-hydroxysteroids) measured in urine
How is a dexamethasone suppression test carried out?
How does it work?
What response might someone with Cushing's have?
Patient given oral Dexamethasone that suppresses ACTH and therefore cortisol secretion. Cortisol levels then monitored.
If cortisol is suppressed by >50% this is characteristic of Cushing's as even though the disease pituitary is relatively insensitive to cortisol, it does retain some sensitivity to potent synthetic steroids.
Suppression will not occur in adrenal tumours or ectopic ACTH secretion
Normal response will exclude Cushing's disease
What is the Synacthen test and why is it carried out?
What response is normal and what indicates abnormality?
Administration of Synacthen (synthetic analogue of ACTH) via intra muscular injection
This normally increases the plasma cortisol by >200nmol/L
Abnormal response indicates Addison's disease, normal response rules this out.
Explain the structure of Steroid receptors
What class of proteins do these receptors belong?
What other types of receptors are in this class of proteins?
Steroid receptors are Nuclear DNA binding proteins
They include 3 main regions:
- Hydrophobic hormone binding region
- DNA binding region
- Variable region
This class of proteins also includes Thyroid and vitamin D receptors