WEEK 4: Adrenal Flashcards
Each adrenal gland is made up of which two distinct parts?
Adrenal cortex: outer part of gland which produces hormones that are vital to life.
Adrenal medulla: inner part of gland which produces non-essential hormones. This does not mean that these hormones are not important – it just means that our lives do not depend on them.
Which part of the adrenal gland produces hormones involved in the fight-or-flight response?
The adrenal medulla
Which part of the adrenal gland produces steroid hormones?
The adrenal cortex
The adrenal medulla is comprised of … cells that secrete …, mainly adrenaline and noradrenaline, but also dopamine.
chromaffin
catecholamines
The adrenal cortex comprises about …% of the adrenal gland
80
The adrenal cortex can be subdivided into what three layers?
Zona glomerulosa
Zona fasciculata
Zona reticularis
Gonadal steroids can be subdivided into what three sections?
progestogens, oestrogens, and androgens.
Steroid hormones can be grouped into what three families with structural and biological similarities?
Gonadal or sex steroids, glucocorticoids and mineralocorticoids
What is the most important mineralocorticoid?
aldosterone
Mineralocorticoids affect … or … concentrations
mineral or electrolyte concentrations.
What is the precursor of all steroid hormones?
Cholesterol
How can cholesterol be synthesised within cells? (adrenal or gonads)
- from acetate
- from Low Density Lipoprotein (LDL) uptake from blood, via LDL receptor-mediated endocytosis.
What is the intermediate precursor between cholesterol and steroid hormones.
pregnenolone (NOT a hormone)
The highest level of the cholesterol side-chain cleavage system is found in the ……
adrenal cortex, the ovaries and testes.
Name the the major steroid hormone producing glands in the body
the adrenal cortex, the ovaries and testes.
… is the rate limiting enzyme in all steroid hormone production.
Cytochrome P-450scc
T or F
androgens can be converted into oestrogens.
T
After cholesterol is converted to progestogens, what are the progestogens then converted into?
either androgens or glucocorticoids.
Aldosterone is only produced in the zona …
glomerulosa.
T or F
Cortisol can bind strongly to mineralocorticoid receptors.
F
weakly
Why is aldosterone only produced in the zona glomerulosa?
Cells in this layer express the enzyme aldosterone synthase - which converts corticosterone to aldosterone.
T or F
corticosterone, cortisol and aldosterone differ only slightly in structure
T
The main steroid hormones secreted by the adrenal cortex are:
Aldosterone, cortisol, corticosterone, DHEA and androstendione.
T or F
Mineralocorticoids and glucocorticoids are exclusively secreted by the adrenal cortex
T
What layers of the adrenal cortex produce mineralocorticoids and glucocorticoids?
They are produced by the zona fasciculata and zona reticularis layers.
Aldosterone is formed from …, … and …
cholesterol, progesterone and corticosterone
What is the most common glucocorticoid in humans?
Cortisol
The sex steroids include
a) Glucocorticoids
b) Androgens
c) Oestrogens
b
The HPA axis includes a group of hormone-secreting glands from the … and … systems.
nervous and endocrine
What glands are part of the HPA axis?
The hypothalamus, pituitary, and adrenal glands.
What is the primary function of the HPA?
To regulate the stress response.
The … and … act together to regulate the adrenal cortex.
hypothalamus and anterior pituitary
The … and … act together to regulate the adrenal cortex.
hypothalamus and anterior pituitary
When ACTH circulates to the adrenal gland it acts to …
- Increase hormone synthesis and secretion by the adrenal cortex.
- Increase the size of the adrenal gland.
What is the main hormone that ACTH stimulates from the adrenal gland?
cortisol
T or F
ACTH has little or no effect on aldosterone secretion.
T
Cortisol exerts long-loop negative feedback effects on both the … and … to regulate the HPA axis.
hypothalamus (CRH neurons) and the anterior pituitary (corticotroph cells)
There is an increase in the hormones …, … and … in response to a stressor.
CRH, ACTH and cortisol
T or F
The HPA axis is only activated by psychological stress not physiological (e.g. hunger)
F
ACTH binds to …… receptors on adrenal cortical cells.
plasma membrane
ACTH stimulates steroidogenesis in which ways?
increases cholesterol uptake and trafficking
increases pregnenolone production
increases expression key enzymes eg. P-450scc (side chain cleavage), P-450c11 (11-beta hydroxylase)
T or F
ACTH has the most effect on the mineralocorticoid aldosterone.
F
ACTH has no effect on the mineralocorticoid aldosterone.
What is the phrase “cortisol awakening response” referring to?
Cortisol increases markedly when you wake up and this is called the “cortisol awakening response”.
cortisol declines during the day, from morning to evening, and this is called the …
diurnal “cortisol slope”.
Circulating cortisol concentrations follow a pattern throughout the day. What structures are responsible for controlling this rhythm?
Central endogenous clock, Hypothalamus and Hypothalamic suprachiasmatic nucleus.
The hormone-receptor complex ends up binding to specific regulatory elements on DNA called ……. to regulate gene transcription.
hormone response elements
What is the first step of glucocorticoid signaling?
Cortisol enters cells via diffusion as it is lipophilic. It binds to the glucocorticoid hormone receptor (GR) in the cytoplasm, forming a hormone-receptor complex.
What is the role of a heat shock protein in glucocorticoid signaling?
the heat shock protein acts to stabilise the glucocorticoid receptor when it is not bound to cortisol.
Binding of cortisol causes what to happen to the hormone-receptor complex during glucocorticoid signaling?
Binding of cortisol causes the receptor to dissociate from a chaperone hsp-90 (90 kDa heat shock protein).
In glucocorticoid signaling the hormone-receptor complex translocates to the nucleus, where it binds to what is known as a ….
glucocorticoid response element (GRE)
What is a glucocorticoid response element (GRE)?
A nucleotide sequence in the DNA upstream of the gene transcription start site in the promotor region. Which responds to the hormone-receptor complex.
T or F
The outcome of binding of the hormone-receptor complex on genes is always negative, repressing transcription.
F
The outcome of binding of the hormone-receptor complex on genes may be positive or negative, either activating or repressing transcription (depending on the gene and cell).
Overall in a stress response cortisol increases…, … and … which can all be oxidised to provide metabolic energy.
fatty acids, amino acids and glucose
T or F
Small amounts of glucocorticoids are required for all metabolic reactions to occur.
F
Small amounts of glucocorticoids are required for some metabolic reactions to occur.
glucocorticoids are necessary for catecholamines to exert their … and … responses.
lipolytic effects (metabolic reactivity. increasing fatty acids as an alternative energy supply.) and increased blood pressure responses (vascular reactivity).
glucocorticoids in pharmacological concentrations can reduce …
inflammation
By regulating electrolyte balance, mineralocorticoids are very important in determining ……, and therefore ……
fluid volumes
blood pressure
Aldosterone acts directly on the … of the … in the kidneys to increase reabsorption of … back into the blood.
distal convoluted tubule
nephrons
sodium ions
aldosterone stimulates the secretion of … into the tubular lumen, promoting loss of … in urine.
potassium ions
potassium ions
What are the 3 regulators of aldosterone synthesis?
ACTH (only a weak effect)
Angiotensin II
Plasma K+ concentrations
T or F
Like glucocorticoids, aldosterone is directly regulated by ACTH.
F
Unlike glucocorticoids, aldosterone is not directly regulated by ACTH.
Why is ACTH considered only a weak stimulator of aldosterone?
because it stimulates the production of precursor hormones.
The main regulator of aldosterone is …
the hormone angiotensin II
The hormone angiotensin II is part of what hormone cascade?
The hormone cascade called the Renin-Angiotensin-Aldosterone-System (RAAS).
T or F
Aldosterone acts directly on the distal convoluted tubule of the nephron to increase reabsorption of Na+ into the blood.
T
T or F
Angiotensin II is an enzyme.
F
It is a hormone.
Symptoms of underactive adrenal glands include…
fatigue, weight loss, poor appetite, weakness and gastrointestinal problems.
Disorders that result in underactive adrenal glands include…
Primary adrenal insufficiency (Addison’s disease)
Secondary adrenal insufficiency
Congenital adrenal hyperplasia
Polyglandular autoimmune syndrome Type 1 and Type 2
Pheochromocytoma, a rare, usually benign, tumour of the adrenal glands resulting in the glands secreting excessive amounts of the hormones adrenaline and noradrenaline (catecholamines) can cause various symptoms including…
high blood pressure, sweating, headache, chest pain and anxiety.
Are glucocorticoids lipid soluble?
Yes
Most cortisol in the blood is bound to a carrier protein called…
cortisol-binding globulin
T or F
Cushing’s syndrome is any condition that causes increased levels of cortisol
T
What are the two types of causes of Cushing’s syndrome or disease?
Exogenous (drug related)
Endogenous (pituitary tumor, adrenal tumour, excess ACTH
When Cushing’s syndrome is caused by a pituitary adenoma making excess ATCH it is called?
Cushing’s disease
T or F
Only cortisol bound to cortisol-binding globulin is biologically active
F
Only cortisol unbound to cortisol-binding globulin is biologically active.
What percentage of cortisol is unbound to cortisol-binding globulin?
5%
In stress, cortisol increases…
Gluconeogenesis - synthesis of new glucose molecules
Proteolysis - breakdown of protein
Lipolysis - breakdown of fat
When the zona glomerulosa is destroyed Aldosterone falls causing what to happen to the bloods potassium and sodium levels?
Hyperkalemia (high K+)
Hyponatremia (low Na+)
T or F
Addison’s disease causes the zona glomerulosa to deteriorate.
F
Not necessarily, the symptoms of Addison’s disease depend on the layers of the adrenal gland affected.
What happens if Addison’s disease causes the zona fasciculata to be destroyed?
Cortisol lvls fall causing:
- low blood glucose in times of stress
- the pituitary gland can become overactive. Causing too much proopiomelanocortin to be produces.
What happens if Addison’s disease causes the zona reticularis to be destroyed?
Androgen lvls fall which doesn’t affect men much as their testes compensate. Women however may experience a loss of pubic and armpit hair and a decreased sex drive
What’s another word for primary aldosteronism?
Conn’s syndrome.
Lists symptoms of Conn’s syndrome
Muscle weakness, fatigue, difficulty concentrating, polyuria, diastolic hypertension, polydipsia, increased renin, hypokalaemia
Primary aldosteronism usually causes … blood pressure and … potassium (K+) blood levels.
high
Low
T or F
Drug treatment for adrenal excess is rarely of benefit but may be used short-term
T
Define Adrenal Suppression
Adrenal Suppression: this refers to the ACT of suppressing the adrenal gland, i.e., the inadequate adrenal production of cortisol due to suppression of the hypothalamic-pituitary-adrenal (HPA) axis.
Define Adrenal insifficiency
Adrenal Insufficiency: this refers to the clinical consequences of suppressing the adrenal gland. This may occur, for example, when there is too rapid tapering or cessation of exogenous glucocorticoids or withdrawal from endogenous glucocorticoid excess (e.g., following treatment of Cushing’s disease or an adrenal tumour causing Cushing’s syndrome).
How is adrenal insufficiency detected?
Adrenal insufficiency is detected by observing clinical signs and symptoms.
What is adrenal insufficiency?
a condition in which the adrenal glands do not produce adequate amounts of steroid hormones, primarily cortisol; but may also include impaired production of aldosterone.
Adrenal insufficiency can also be called…
adrenal crisis
What are some symptoms of chronic adrenal insufficiency?
Poor stress response, constipation and diarrhea, weakness, pigmentation of skin, hypotension, weight loss, nausea and vomiting
What are some symptoms of acute adrenal insufficiency?
shock, hyperkalemia, hypoglycemia and severe hypotension