Adrenals and Stress Hormones: Bridges

Question 1

Name three zones in the adrenal cortex and major regulator(s) of each zone.

Answer 1

Zona glomerulosa- aldosterone (angiotensin II)
Zona fasciculata- Cortisol and small amount of androgens (ACTH)
Zona reticularis- Androgens and small amount of cortisol (ACTH)

Question 2

Name three steroidogenesis pathways and their major products.

Answer 2

Specific steroid hormones are synthesized from cholesterol via enzymes which are regulated by GPCR mediated signaling. In response to the synthetic signal*, the GPCR’s are activated resulting in cAMP/PKA or IP3 signaling cascades.
*Synthetic signals:
ACTH for cortisol
AT II for aldosterone
ACTH for Dehydroepiandrosterone and Androstenedione (Testosterone)

1) Mineralcorticoid pathway- aldosterone
2) Glucocorticoid pathway- cortisol
3) Androgen and estrogen pathway- DHEA and androstenedione —> testosterone

Not steroids, but: Epi and NE are secreted by the adrenal medulla in response to neuronal signaling by the sympathetic NS.

Question 3

Describe the physiological actions and roles of aldosterone.

Answer 3

Aldosterone, which is a mineralcorticoid, is primarily responsible for sensing and modulating salt balance at the kidney.

The mineralcorticoid receptor binds to aldosterone, which
then promotes the transcription of three important genes involved in salt reuptake:
::Sodium/potassium pumps. These pumps exchange sodium for potassium, to move sodium out of the kidney and back into the blood.
::ENac This is a sodium transporter that helps get sodium from the tubule into the cells of the collecting duct.
::SGK1 Is a protein kinase that activates several transporters by posttranslational
modification.

Question 4

Explain briefly the renin-angiotensin system.

Answer 4

The kidney produces renin that converts angiotensinogen (produced by liver) to angiotensin I. Angiotensin converting enzyme (ACE), secreted by endothelial cells, then converts angiotensin I –> angiotensin II (AGII).
The AGII then acts on the CV system to constrict BVs and the kidney both directly and indirectly (via aldosterone from adrenal cortex) to reabsorb water and sodium. This results in ^ BP.

Question 5

Describe the negative feedback regulation of aldosterone and its relationship to blood volume/blood pressure homeostasis.

Answer 5

Once salt balance, blood volume and blood pressure are renormalized, renin release is reduced, causing less angtiotensin I formation and therefore less aldosterone production.

Question 6

Describe hepatic and extrahepatic metabolic actions of glucocorticoids. Discuss their relationship.

Answer 6

A second major role of cortisol is to suppress immune
function.
Cortisol functions at several steps in the immune
response, including suppressing both the innate and adaptive immune system.

In addition to its direct effects, cortisol also sensitizes
tissues to epinephrine, so that short-term stress responses can also be activated in times of chronic stress. This is accomplished by the glucocorticoid receptor directly activating the transcription of the b-adrenoreceptor gene

Question 7

Name the major hormones secreted from the adrenal medulla. Discuss the differences of epinephrine (epi) and norepinephrine (NE) in cardiovascular actions (physiological levels).

Answer 7

• The adrenal medulla secretes epinephrine and norepinephrine, two water soluble biogenic amines also known as adrenaline and noradrenaline.
• Adrenaline is released via direct sympathetic innervation of the adrenal medulla.

Under most physiological conditions including hypoglycemia or moderate exercise, norepinephrine levels do not rise in the plasma to a level which would activate the adrenergic receptors. The two situations where this may occur are during very heavy exercise or tumors which secrete norepinephrine

Circulating Norepinephrine Causes:

Increased heart rate (although only transiently) and increased inotropy (β1-adrenoceptor mediated) are the direct effects norepinephrine on the heart.
Vasoconstriction occurs in most systemic arteries and veins (postjunctional α 1 and α 2 adrenoceptors)
The overall cardiovascular response is increased cardiac output and systemic vascular resistance, which results in an elevation in arterial blood pressure. Heart rate, although initially stimulated by norepinephrine, decreases due to activation of baroreceptors and vagal-mediated slowing of the heart rate.

Question 8

List the major metabolic actions of catecholamines.

Answer 8

Make more blood glu available in times of stress.
In contrast to the slower acting cortisol, adrenaline promotes rapid breakdown of glycogen and triglycerides to make their products available for muscle oxidation.

Epi induces lipolysis so skeletal muscle will have FFA to feed off of (oxidize) in an emergency instead of their own AAs. This is not found in stress responses by cortisol.

In the liver, where most of the body’s glycogen is stored,
b-adrenergic receptor activation of PKA results in the activation of glycogen phosphorylase and inhibits glycogen synthase.

Activation of PKA also increases gluconeogenesis and transcription of gluconeogenesis genes.

In muscle tissue, PKA activation via a Gs linked b-adrenergic receptor induces glycogenolysis, glycolysis and mitochondrial respiration to generate ATP for muscle contraction.

Question 9

Contrast the thresholds for actions vs. plasma levels of epi and NE under common conditions, like exercise, and in the disease pheochromocytoma.

Answer 9

The circulating levels of norepinephrine are low, relative
the the amount needed to elicit an adrenergic response. This is because in many cases, norepinephrine is utilized synaptically where the local concentrations can be very high.
Under most physiological conditions including hypoglycemia or moderate exercise, norepinephrine levels do not rise in the plasma to a level which would activate the adrenergic receptors. The two situations where this may occur are during very heavy exercise or tumors (pheochromocytoma) which secrete norepinephrine.
Clinically these patients have elevated heart rate, blood pressure and anxiety and undergo rapid weight loss and elevated blood glucose.