Endocrine 07, 08 - Adrenal Steroid Hormones
Terms
undefined, object
copy deck
- What is the precursor of all steroid hormones?
- Cholesterol.
- How is cholesterol transported from the liver to the adrenal gland (and gonads and placenta)?
- LDL.
- Name the 3 zones of the adrenal cortex (from capsule to medulla).
-
1) Glomerulosa
2) Fasciculata
3) Reticularis - Which steroid hormone is produced in the zona glomerulosa?
- Aldosterone (mineralocorticoids).
- Which steroid hormone is produced in the zona fasciculata?
- Cortisol (glucocorticoids).
- Which steroid hormones are produced in the zona reticularis?
- Androgens (DHEA, Testosterone, Estrogen, Androstenedione, Progesterone).
- What is the function of cortisol (glucocorticoids)?
- Increase plasma blood glucose by activating gluconeogenesis, and inhibiting insulin.
- What is the function of aldosterone (mineralocorticoids)?
- Increase Na+ retention and therefore water retention and blood pressure.
- What is the function of androgens?
- Development of secondary sexual characteristics, etc.
- To which cell layer does ACTH bind to in the adrenal cortex, and what is the ensuing product?
- Plasma membrane of cells in the zona fasciculata, producing cortisol.
- To what cell layer of the adrenal cortex will Angiotensin-II bind, and what steroid hormone will be produced?
- Zone glomerulosa, producing aldosterone.
-
What is the rate-limiting step of cortisol, aldosterone, and DHEA biosynthesis, where does it occur, and by what enzyme?
What stimulates this conversion? -
Cholesterol --> pregnenolone.
Mitochondrial membrane.
Cyp450(scc).
ACTH. - Which family of enzymes are critical in the formation of all steroid hormone biosynthesis?
- CypP450 enzymes, which hydroxylate intermediates.
- Steroid hormone products of the adrenal cortex are synthesized and secreted _________, not ________.
- on demand; stored.
- Which hormone secreted by the female ovaries, is only a transient intermediate in the adrenal cortex?
- Progesterone.
- Pregnenolone branches into what 2 products?
-
1) Progesterone (transient)
2) DHEA - reticularis -
Progesterone branches into what 2 products?
What enzymes motivate this conversion? -
1) Aldosterone - glomerulosa
2) Cortisol - fasciculata
Cyp450 (c21 and c11 respectively) - What effect does an increase in cortisol have on the hypothalamus/pituitary hormone pairs?
- Negative feedback control on the hypothalamus, decreasing CRH/ACTH release - and vice versa.
-
What substrate is critical in the functioning of cortisol?
What enzyme facilitates this? -
11-OH group is critical for physiological activity.
Cyp450(c11). - What is the effect of cortisone?
- Anti-inflammatory steroid.
- In aldosterone, what substrate-specific reaction occurs that is important for kidney action?
- Tying up the 11-OH group to form a hemiacetal.
- What is Congenital Adrenal Hyperplasia (CAH)?
-
Deficient Cyp450(c21)
Block aldosterone and cortisol pathways
Back up the reticularis pathway
Increase androgen output (male sex hormones) - What is the cause of Congenital Adrenal Hyperplasia (CAH)? What test is used to diagnose it?
- Deficient Cyp450(c21). Inject ACTH and observe a rise in 17-OH-Progesterone, which gets backed up when Cyp450(c21) is deficient.
- What are the clear clinical characteristics of CAH and in whom are they most clearly observed?
- Ambiguous genitalia and hirsutism seen clearly in female infants.
- Where are weak androgens converted to strong androgens?
- Liver, muscle, adipose tissue.
- What function do strong androgens play in the female?
- Major source of testosterone in females, maintain secondary sexual characteristics, are the sole estrogen precursors.
- Describe how cortisol is secreted by the adrenal cortex (in an unstressed individual)?
- Pulsatile bursts.
- What is significant about Pro-opiomelanocortin (POMC)?
- It derives into ACTH; ACTH production will also result in MSH and opioid formation.
- How does cortisol respond to different levels of stress?
-
Major stress - cortisol rises steeply.
Minor stress - cortisol rises, but not as much. - What stimulation test is used to confirm hypopituitarism with respect to the secretion of cortisol?
- Insulin injection will cause neither ACTH nor cortisol to rise in response to increased plasma glucose levels.
- How is cortisol transported in plasma?
- 80% is bound to CBG (Cortisol Binding Globulin), 15% bound to albumin, and 5% is free and active.
- How is aldosterone transported in plasma?
- 60% is bound to albumin (no globulin transporter), and the rest is free since it is more water soluble than cortisol.
- Between cortisol and aldosterone, which has a faster turnover rate?
- Aldosterone.
- Where are cortisol and aldosterone catabolized?
- In the liver.
- What structures of aldosterone and cortisol are preserved during catabolism?
- Steroid nucleus. Side groups are conjugated and inactivated for secretion.
- What molecule can be measured as an indicator of cortisol secretion?
- 17-OH-corticoids.
- True/False: Cortisol is required for survival.
- True.
- What processes does cortisol stimulate?
-
1) Liver gluconeogenesis
2) Fat lipolysis - What hormone does cortisol block?
- Insulin.
- What counterintuitive process occurs during cortisol secretion?
- Glycogen synthesis. Cortisol causes some glucose to be released into the circulation, and some to store as glycogen.
- *Increased insulin will suppress gluconeogenesis and glycogenolysis. How will cortisol affect these processes?
- More insulin is required in the presence of cortisol for insulin to have the same effect.
- Increased insulin will increase glucose uptake from the circulation. How will cortisol affect this process?
- It will require more insulin to take up the same amount of glucose. Sometimes cortisol results in hyperglycemia.
- *How does cortisol affect host defense mechanisms?
-
1) Supresses inflammation (cortisone), usually in response to long-term stress, by blocking phospholipase A2, which blocks the formation of leukotrienes and prostaglandins.
2) Suppresses immune response (block cytokine release, block fever cytokines, block T and B cell proliferation) - True/False: Aldosterone is necessary for survival.
- True.
- How will the kidney respond to a low circulating blood volume and pressure?
- RAA pathway: Renin is released converting AT --> AT-I and ACE is released to convert AT-I --> AT-II.
- What are the main functions of AT-II?
-
1) Regulation of aldosterone synthesis
2) Vasoconstriction
In response to low blood pressure/volume. - What plasma ion concentration is critical in aldosterone regulation?
- Potassium.
- How is essential hypertension and edema typically treated?
- ACE inhibitors to lower the synthesis of aldosterone.
- How do steroid hormones act on the nucleus?
- Hormones bind to their receptors, which will transform into transcription factors and enter into the nucleus.
- *What types of dimers are formed by steroid hormone receptors as they act as transcription factors? How will they act on DNA?
-
Homomeric dimers.
Induce transcription by recruiting RNA polymerase, but sometimes suppress it. - Steroid hormone receptors may interact with transcription factors in 3 ways. Describe them.
-
1) Homomeric dimer can bind to a positive HRE, inducing transcription.
2) Homomeric dimer can bind to a negative HRE, suppressing transcription.
3) Homomeric dimer can bind directly to the positive transcription factor itself, suppressing transcription. - Describe how cortisol induces anti-inflammatory effects.
-
Cortisol binding will induce the transcription of anti-inflammatory protein Lipocortin-1, which inhibits phospholipase A2, which blocks formation of leukotrienes and prostaglandins. An IL-1 antagonist will also form.
The pro-inflammatory TF NF-κβ is also inhibited. - *What is the bodyguard protein (11β-HSD)?
- Due to the high structural similarity between cortisol and aldosterone, the bodyguard protein prevents cortisol from binding to aldosterone receptors, which would cause hypertension.
- What molecule will inhibit the bodyguard protein (11β-HSD)?
- Glycyrrhetinic Acid, GA, (found in licorice), and will induce hypertension.
- What is primary Cushing's Syndrome? What is its distinctive feature?
- An adrenal cortex adenoma or carcinoma resulting in hypersecretion of cortisol. The distinctive feature is a DROP in ACTH levels.
- What is secondary Cushing's Syndrome?
- Also known as Cushing's DISEASE, this is a hypersecretion of Cortisol due to moderately excessive pituitary output of ACTH.
- What is Ectopic ACTH Syndrome?
- Hypersecretion of cortisol due to increased ACTH from sources other than adrenal cortex or pituitary (lung cancer).
- What are the symptoms for Cushing's?
- Moon-shaped face, muscle wasting, increased facial hair, blood vessel thinning, thin skin.
- How would you differentiate a hypersecreting cortisol disorder?
-
High Cortisol, Low ACTH - Primary Cushing's (adenoma)
If High Cortisol AND High ACTH:
High dose of DEX resulting in suppression of ACTH - Secondary Cushing's.
High dose of DEX resulting in NO suppression of ACTH - Ectopic ACTH Syndrome.
Low dose of DEX resulting in suppression rules out Cushing's. - What is primary Addison's Syndrome?
- Also known as Addison's DISEASE, adrenal cortex (target organ) failure results in low levels of cortisol.
- What is secondary Addison's Syndrome?
- Deficiency in the pituitary gland, resulting in low cortisol levels.
- What is tertiary Addison's Syndrome?
- Deficiency in the hypothalamus, resulting in low cortisol levels.
- What are the symptoms for Addison's?
-
High levels of ACTH and MSH (hyperpigmentation) in Primary Addison's.
Low levels of ACTH (pale skin and inability to tan) in Secondary and Tertiary Addison's. - How do you test for Addison's?
-
If plasma cortisol is low, administer ACTH to the adrenal cortex. No cortisol production - Primary Addison's.
Cortisol produced - Secondary or Tertiary Addison's. - When do you measure cortisol?
- 8 AM, when the level is highest.
- What hormone pair does an injection of insulin affect?
- CRH/ACTH will increase in a normal individual.
- What effect does cortisol have on the bone and connective tissue?
- Decrease bone formation and increase bone resorption; decrease connective tissue - typical in osteoporosis.