4.2 Adrenal steroids Flashcards
What is the outside and inside of the adrenal gland called?
Outisde = adrenal cortex
Inside = adrenal medulla
The adrenal cortex is under the control of what?
The anterior pituitary gland
Name the 3 morphologically distinct zones of the adrenal cortex from the most external to most internal.
- Zona Glomerulosa (mineralocorticoids)
- Zona Fasciculata (glucocorticoids)
- Zona Reticularis (gondocorticoids)
What causes the cortex to have these 3 distinct zones?
Presence of different enzymes.
Name a mineralocorticoid.
Aldosterone
Name a glucocorticoid.
Cortisol
All of the hormones produced by the adrenal cortex are ……. hormones.
Steroid hormones
Synthesis of these steroid hormones are under the control of which family of enzymes?
The P450 superfamily of enzymes.
Most diseases caused by a deficiency in steroid hormones are caused by an enzyme deficiency.
What are the 2 effects of enzyme deficiency?
- Steroid hormone deficiency
- Excess precursor compounds (used in diagnostic testing)
Which enzyme is crucial in the conversion of cholesterol to an adrenal steroid?
Cholesterol desmolase
What regulates cholesterol desmolase activity?
Cholesterol desmolase activity is tightly regulated by ACTH and angiotensin II.
Are steroid hormones stored in vesicles?
No, as they are derived from cholesterol they are highly lipophilic so cannot be stored in vesicles.
Where does adrenal steroid synthesis occur?
In the mitochondria, some later steroids form in the endoplasmic reticulum.
Describe the action of adrenal steroid hormones.
Work at the level of gene expression.
Typically act through modifying gene transcription.
What effect does it have that adrenal steroids work at the level of gene expression?
- Means that the pharmacodynamic effects are much longer than the pharmacokinetics of the drug
- Means that there is a latency period between drug administration and seeing physiological effects
Where are adrenal steroids metabolised?
In the liver (heaptic metabolism)
What occurs after adrenal steroids are metabolised?
They undergo conjugation with glucuronic acid or sulphates and are excreted through urine.
What are the potential targets of pharmacological drugs in steroid action?
- The secretagogue: similar action to the hormone itself. Can create agonists which mimic the action of hormones, or antagonists which can block the effect of hormones.
- The enzymes required for synthesis of hormones.
- Deliver the hormone itself.
- Drugs to target the drug receptor, or a co-factor for the target receptor.
Which enzyme controls the conversion of pre-aldosterone to aldosterone?
Aldosterone synthase
Where does the conversion of pre-aldosterone to aldosterone occur?
In the Zona Glomerulosa
How are patients with low aldosterone treated?
- Excessive salt and water replacement
- Delivery of exogenous mineralocorticoids
Describe the actions/functions of aldosterone.
- Maintains sodium/potassium balance
- Regulates ECF volume, in turn regulates BP
- Minor role in regulating acid/base balance through H+/K+ exchange
- Some role in repairing tissue damage
What are the main secretagogues involved in increasing aldosterone synthase?
- Angiotensin II
- Extracellular potassium concentration (higher K = higher aldosterone)
- ACTH
- Paracrine factors
What is familial hyperaldosteronism I?
A genetic condition
- Gene mutation causes excess aldosterone
- Leads to hypertension
- Treated with glucocorticoids to suppress ACTH
