Lesson 8 HR Adrenal glands and glucocorticoids

Where are the adrenal glands located?

Near the thoracolumbar junction and craniomedial to the kidneys

What is the relative shape of the adrenal glands?

Asymmetrical or irregularly shaped

What are the two main layers of the adrenal glands?

cortex

medulla

What is the cortex in the adrenal glands?

The cortex is outer most layers of the adrenal gland. It is divided into three zones that have specific enzymes that allow them to produce different steroid hormones.

What are the three different zones of the cortex?

Zona Glomerulosa

Zona Fasciculata

Zona reticularis

What hormone is produced in the zona glomerulosa zone?

Aldosterone

What hormone is produced in the zona fasciculata?

Cortisol

What hormones are produced in the zona reticularis?

Androgens (sex hormones)

What are the medullary cells called due to their affinity for chromium and other heavy metals?

Chromaffin cells

The adrenal gland are primarily innervated by what type of nerves?

Pre-ganglionic sympathetic nerves

What is secreted by the chromaffin cells of the adrenal medulla?

Epinephrine

What stimulates the epinephrine production in the adrenal medulla?

Cortisol

How does the chromaffin cells receive the cortisol from the cortex?

Via portal veins

What is the key enzyme in the synthesis if steroid hormones?

3-B Hydroxysteroid Dehydrogenase

Why is it important that the adrenal cortex is highly vascularized?

Hormones produced in the cortex are immediately released into circulation

What is the main stimulus for cortisol secretion?

stress

What is another name for cortisol?

Glucocorticoid

What are the other stimuli of cortisol secretion?

Pain

Pyrogens

infections

illness

epinephrine

histamine

hypoglycemia

Secretion of cortisol is under the control of what?

Hypothalamic-pituitary axis

Under the influence of stimulus the hypothalamus will release what to promote cortisol secretion?

Corticotropin releasing hormone (CRH)

What happens when CRH reaches the anterior pituitary which stimulates the release of what?

Adreno-corticotropic hormones (ACTH)

When ACTH is released into the systemic blood circulation and acts on target cells of the adrenal cortex where it stimulates what?

The synthesis and release of cortisol

What is the steroid hormone that circulates in the blood mostly bound to transport proteins/

Cortisol

When cortisols increase exerts what type of feedback on both the release of CRH and ACTH?

Negative feedback

Most tissues on the body have receptors for cortisol, and cortisol is lipiphilic which mean the receptor is where?

Intracellularly in the cytoplasm

Once the cortisol receptor complex is formed what does it stimulate?

a change in gene expression

What are the general function of cortisol?

regulates metabolism

increases during stress

Decreases the immune response

Promotes heart and vasomoter effects

How does cortisol effect the liver?

Increased gluconeogenesis

How does cortisol effect the muscle?

Decreases glucose uptake and increases proteolysis

How does cortisol effect the adipose tissue?

stimulates lipolysis

How does cortisol effect the pancreas?

Increase glucagon release

How does cortisol effect the immune system?

Apoptosis of T-cells and inhibits Antibodies production of B-cells

Decreases lymphocytes and eosinophils

What is it called when the body produces an excessive amount of cortisol?

Hyperadrenocorticism aka Cushings Disease

What are the effects of excessive cortisol on the muscles?

Proteolysis induces muscle wasting and weakness

What are the effects of excess cortisol production on the bones?

Decreased Ca+ absorption from intestines

Increased Ca+ excretion by the kidneys

Skeletal mass decreases and bones become weaker

What is the effect of excess cortisol on skin?

Protein catabolism results in thin and inelastic skin, poor skin healing, and poor scar formation

Calcinosis cutis

What are the effects of excess cortisol on the cardiovascular system?

Increases sensitivity to catecholamines by increasing beta-adrenergic receptors which can lead to hypertension.

What is the effect of excess cortisol on the GI tract?

Increases appetite and food intake

Stimulates HCL secretion while reducing mucus production leading to ulcers

What is the effect of excess cortisol on the liver?

Liver enlargement

Lipolysis and fat mobilization

Glycogen synthesis and accumulation in the liver

What is the effect of excess cortisol in the adipose tissue?

Lipolysis induced by cortisol releases fatty acids that are stored in unusal areas (fat pads)

What is the effect of excess cortisol on body weight?

Weight loss due to lipolysis and proteolysis driven

What are the 5 P’s due to excessive cortisol production?

Pot belly (pendulous abdomen)

Panting

PU

PD

Polyphagia

What are the three other P’s from excessive cortisol?

Dermatologic problems

Hypertension

Bilateral Alopecia (due to shortedn anagen phase and premature catagen)

What drug is used to treat Cushings?

Enzyme inhibition therapy: Trilostane

What is the therapeutic goal of trilostane?

Reduce the excessive production of cortisol

What is the therapeutic target and mechanism of action of trilostane?

Competitive and reversible inhibition of 3B-hydroxysteroid dehydrogenase