Adrenal-gland Hormones Flashcards
In the adrenal gland, where are norepinephrine & adrenaline synthesized?
Norepinephrine & adrenaline are catecholamines (amine hormones, derived from tyrosine), which are produced in the adrenal medulla.
Form superficial to deep, what are the three zones of the adrenal cortex?
(capsule)
Zona glomerulosa
Zona fasciculata
Zona reticularis
(medulla)
What type of hormone is synthesized in the Zona glomerulosa of the adrenal cortex?
Mineralcorticoids, a class of steroid hormones. Most importantly, aldosterone.
What is aldosterone, where is it made and what does it do?
Aldosterone is a steroid hormone of the mineralcorticoid class, produced from cholesterol, like all steroid hormones. It is synthesized by the zona glomerulosa cells in the outer band of the adrenal cortex of the adrenal gland.
It acts mainly on the distal tubules and collecting ducts of the kidney nephron to cause the conservation of sodium, secretion of potassium, increased water retention, and increased blood pressure.
The overall effect of aldosterone is to increase reabsorption of ions and water in the kidney – increasing blood volume and, therefore, increasing blood pressure.
Aldosterone has exactly the opposite function of the atrial natriuretic hormone secreted by the heart.
What type of hormone is produced in the zona fasciculata of the adrenal cortex?
Glucocorticoids, a class of steroid hormones, is produced by the zona fasciculata cells in the largest, middle band of the adrenal cortex.
Cortisol is the most important glucocorticoid secreted by the zona fasciculata.
NB In rodents, corticosterone, not cortisol, is secreted by the zona fasciculata. Corticosterone is also a glucocorticoid hormone.
What type of hormone is made in the zona reticularis of the adrenal cortex?
Adrenal androgens, aka adrenal sex hormones.
Zona glomerulosa cells in the adrenal cortex are:
a. Cuboidal
b. Columnar
c. Squamous
d. Stratefied epithelial
b. Columnar, arranged in irregular cords
Zona fasciculata cells in the adrenal cortex are:
a. Cuboidal
b. Polyhedral
c. Foamy-looking
d. Arranged in irregular cords
b & c
Polyhedral & foamy-looking, due to the cholesterol for glucocorticoid synthesis. They are arranged in STRAIGHT cords radiating out toward the medulla.
Zona reticularis cells of the adrenal cortex are:
a. Larger than zona fasciculata cells
b. Intermediate-sized, between zona glomerulosa and zona fasciculata cells
c. Anastomose with each other
d. Arrange in cords projecting in many directions
b, c & d
Cells within this zone are intermediate in size, arranged in cords that project in many different directions and anastomose with one another.
How is the adrenal medulla innervated?
The adrenal medulla is richly innervated by preganglionic sympathetic fibers. Additionally, small numbers of sympathetic ganglion cells are commonly observed in the medulla. Ganglion cells are round or polygonal with prominent nuclei.
What is the most common cell in the adrenal medulla, and what is it responsible for?
Chromaffin cells.
Synthesis of catecholamines begins with the amino acid tyrosine, which is taken up by chromaffin cells in the medulla and converted to norepinephrine and epinephrine.
Where are catecholamines such as norepinephrine and epinephrine synthesized and how are they released into the bloodstream?
Catecholamines are synthesized by the adrenal gland, specifically from the amino-acid tyrosine taken up by chromaffin cells in the adrenal medulla.
Catalyzed by different enzymes, the tyrosine is converted to DOPA, then dopamine, then norepinephrine & epinephrine.
Norepinephine and epinephrine are stored in electron-dense granules which also contain ATP and several neuropeptides.
Secretion of these hormones is stimulated by Ach release from preganglionic sympathetic fibers innervating the medulla. Many types of “stresses” stimulate such secretion, including exercise, hypoglycemia and trauma.
Following secretion into blood, the catecholamines bind loosely to and are carried in the circulation by albumin and perhaps other serum proteins.
After the catecholamines norepinephrine & epinephrine are secreted into the bloodstream from the adrenal medulla, how do they bind to receptors in target cells, such as skeletal myocytes?
Following secretion into blood, catecholamines bind loosely to and are carried in the circulation by albumin and perhaps other serum proteins.
They bind to adrenergic receptors on the surface of target cells.
These receptors are prototypical examples of seven-pass transmembrane proteins that are coupled to G proteins which stimulate or inhibit intracellular signalling pathways.
In general, what is the effect on target cells of norepinephrine & epinephrine binding to G-protein-coupled receptors on the plasma membrane?
In general, circulating epinephrine and norepinephrine have the same effects on target organs as direct stimulation by sympathetic nerves, although their effect is longer lasting.
Note though that complex physiologic responses result from adrenal medullary stimulation because there are multiple receptor types which are differentially expressed in different tissues and cells.
List the major adrenergic receptors and what types of catecholamines they bind.
Alpha 1 - Epinephrine, Norepinphrine
Alpha 2 - Epinephrine, Norepinphrine
Beta 1 - Epinephrine, Norepinphrine
Beta 2 - Epinephrine
What are the similarities & differences between Alpha 1 & Alpha 2 adrenergic receptors?
Both are G-protein coupled receptors (GPCR), which are transmembrane proteins that pass through the target cell’s plasma membrane seven times.
They both bind to the catecholamines epinephrine & norepinphrine.
Alpha-1 receptors, when bound, increase free calcium within a cell. Its effects include:
- Constriction of smooth muscle
- Vasoconstriction of coronary arteries
- Vasoconstriction of veins
- Decrease motility of smooth muscle in GIT (sympathetic response)
Alpha-2 receptors, when bound, decrease cAMP within a cell. Its effects are inhibitory:
- Supression of release of norepinephrine (noradrenaline) by negative feedback.
- Decrease release of acetylcholine in pre- and post-synaptic nerve terminals
- Inhibition of lipolysis in adipose tissue
- Inhibition of insulin release in pancreas
- Contraction of GIT sphincters
- Decreased secretion from salivary gland
- Relax gastrointestinal tract (presynaptic effect)
What are the similarities & differences between beta-1 & beta-2 adrenergic receptors?
Both are transmembrane, G-protein-coupled receptors that bind catecholamines.
Both bind epinephrine.
Both increase cAMP within the cell, but Beta-2 can be both stimulatory AND inhibitory. Beta-1 is only stimulatory.
Beta-2 only binds epinephrine while Beta 1 binds both norepinephrine & epinephrine.
Beta-1 is stimulatory when it binds to norepinephrine or epinephrine. Actions include:
- stimulate viscous, amylase-filled secretions from salivary glands
- Increase cardiac output
- Increase heart rate in sinoatrial node (SA node) (chronotropic effect)
- Increase atrial cardiac muscle contractility. (inotropic effect)
- Renin release from juxtaglomerular cells.
- Lipolysis in adipose tissue.
Beta-2 can be both stimulatory & inhibitory, depending on where it is located. Actions include:
- Relaxation of smooth muscle in uterus (inhibits labour), GIT (delays digestion) & bronchi & detrusor muscle (delays micturition) - mostly fight-or flight
- Dilation of blood vessels to increase perfusion of organs such as hepatic artery, coronary artery and skeletal muscle (sympathetic effect)
List some of the major effects on the body of the adrenal-medulla catecholamines norepinephrine and epinephrine.
Increased rate and force of contraction of the heart muscle: this is predominantly an effect of epinephrine acting through beta receptors.
Constriction of blood vessels: norepinephrine, in particular, causes widespread vasoconstriction, resulting in increased resistance and hence arterial blood pressure.
Dilation of bronchioles
Stimulation of lipolysis in fat cells: this provides fatty acids for energy production in many tissues and aids in conservation of dwindling reserves of blood glucose.
Increased metabolic rate: oxygen consumption and heat production increase throughout the body in response to epinephrine. Medullary hormones also promote breakdown of glycogen in skeletal muscle to provide glucose for energy production.
Dilation of the pupils
Inhibition of certain “non-essential” processes: an example is inhibition of gastrointestinal secretion and motor activity.
Where is the enzyme 17-alpha-hydroxylase found in the adrenal gland, and what are the major products of its catalysis?
17-alpha-hydroxylase is found in the zona fasciculata and the zona reticulata of the adrenal gland. It is necessary for the synthesis of 17-hydroxypregnenolone and 17-hydroxyprogesterone, which are precursors to cortisol and androgens.
Aldosterone & Cortisol can bind to the same mineral corticoid receptor and the same DNA sequence serves as a hormone response element for the steroid-bound forms of both mineralocorticoid and glucocorticoid receptors.
So, how can aldosterone stimulate specific biological effects when blood concentrations of cortisol are 2000-fold higher than aldosterone?
In aldosterone-responsive cells, cortisol is effectively destroyed, allowing aldosterone to bind its receptor without competition. Target cells for aldosterone express the enzyme 11-beta-hydroxysteroid dehydrogenase, which has no effect on aldosterone, but converts cortisol to cortisone, which has only a very weak affinity for the mineralocorticoid receptor. In essence, this enzyme “protects” the cell from cortisol and allows aldosterone to act appropriately.
Some tissues (e.g. hippocampus) express abundant mineralocorticoid receptors but not 11-beta HSD - they therefore do not show responses to aldosterone because aldosterone is not present in quantities sufficient to compete with cortisol.
What are the major controls of aldosterone secretion from the zona glomerulosa of the adrenal cortex?
Concentration of potassium ions in extracellular fluid: Small increases in blood levels of potassium strongly stimulate aldosterone secretion.
Angiotensin II: Activation of the renin-angiotensin system as a result of decreased renal blood flow (usually due to decreased vascular volume) results in release of angiotensin II, which stimulates aldosterone secretion.
Other factors that increase secretion:
ACTH adrenocorticotropic hormone (short-term stimulation only)
Sodium deficiency.
Factors that suppress aldosterone secretion:
ANP atrial naturetic hormone
High sodium concentration
Potassium deficiency
What is Addison’s disease?
Aka hypoadrenocorticism - deficiency of glucocorticoid (esp. cortisol) and mineralcorticoid (esp. aldosterone)
Without treatment by mineralocorticoid replacement therapy, a lack of aldosterone is lethal, due to electrolyte imbalances and resulting hypotension and cardiac failure.
Most commonly, Addison’s is a result of infectious disease (e.g. tuberculosis in humans) or autoimmune destruction of the adrenal cortex.
Clinical signs:
cardiovascular disease, lethargy, diarrhea, and weakness.
What are glucocorticoid’s (cortisol’s) effects on metabolism?
Stimulation of gluconeogenesis, particularly in the liver: This pathway results in the synthesis of glucose from non-hexose substrates such as amino acids and lipids and is particularly important in carnivores and certain herbivores. Enhancing the expression of enzymes involved in gluconeogenesis is probably the best known metabolic function of glucocorticoids.
Mobilization of amino acids from extrahepatic tissues: These serve as substrates for gluconeogenesis.
Inhibition of glucose uptake in muscle and adipose tissue: A mechanism to conserve glucose.
Stimulation of fat breakdown in adipose tissue: The fatty acids released by lipolysis are used for production of energy in tissues like muscle, and the released glycerol provide another substrate for gluconeogenesis.
What are cortisol’s effects on immune function?
Glucocorticoids have potent anti-inflammatory and immunosuppressive properties.
