L8: Glucocorticoids

Where are the adrenal glands located relative to the kidneys?

Near the thoracolumbar junction, craniomedial to the kidneys

the adrenal glands are a ______ structure

paired

What are the two main structural components of the adrenal gland?

The cortex and the medulla

what hormone does the medulla of the adrenal glands produce?

epinephrine

What surrounds the adrenal cortex?

An external capsule

Which hormones are produced by the zona glomerulosa?

Mineralocorticoids, mainly aldosterone

Which hormones are produced by the zona fasciculata?

Glucocorticoids, primarily cortisol.

What hormones are produced by the zona reticularis?

Sex hormones (androgens)

What does the Salt, Sugar, Sex mnemonic refer to in the adrenal cortex?

Salt = zona glomerulosa; Sugar = zona fasciculata; Sex = zona reticularis.

each zone of the adrenal gland has..

specific intracellular enzymes that convert cholesterol into each specific hormone of that zone

What cells form the adrenal medulla?

Chromaffin cells.

What do chromaffin cells secrete in response to sympathetic stimulation?

Epinephrine predominantly, with small amounts of norepinephrine

How is the adrenal medulla innervated?

By pre-ganglionic sympathetic nerves

how do chromaffin cells receive cortisol from the cortex and what does this do?

• received via portal veins

• stimulates epinephrine production

Which axis regulates cortisol secretion?

The hypothalamic-pituitary-adrenal (HPA) axis.

Which hormone from the hypothalamus initiates the cortisol cascade?

CRH (corticotropin-releasing hormone).

Which pituitary hormone stimulates cortisol synthesis in the adrenal cortex?

ACTH (adrenocorticotropic hormone).

What is the primary glucocorticoid produced by the adrenal cortex?

Cortisol.

3-beta-hydroxysteroid dehydrogenase

key enxyme in the synthesis of steroid hormones that converts pregnenolone to progesterone

what happens once hormones are produced in the cortex?

• immediately released into circulation on demand

• NOT STORED

where does the adrenal cortex capillaries drain into?

venous sinus in the zona reticularis and medulla

what is the main stimulus for cortisol secretion?

stress

besides stress, what are other stimuli for cortisol secretion?

1. pain

2. pyrogens

3. infection

4. illness

5. epinephrine

6. histamine

7. hypoglycemia

what hormone will the hypothalamus release when appropriately stimulated during the process of glucorticoid secretion?

Corticotropin-releasing hormone (CRH)

once CRH reaches the anterior pituitary, what peptide hormone will be stimulated to be released?

Adrenocorticotropic hormone (ACTH)

ACTH is released into…

systemic blood circulaion

what does ACTH stimulate?

cortisol synthesis and release

what is the primary glucocorticoid produced in teh adrenal cortex?

cortisol

what type of hormone is cortisol?

steroid

how does cortisol circulate in the blood?

mostly bound to transport proteins

is cortisol lipohilic or hydrophilic?

lipophilic

in what structure of the cell are glucocorticoid receptors located?

cytoplasm

where do activated cortisol-receptors enter and what is their function?

• nucleus

• affect gene expression

what organ is most important in stressful situations and what hormone is it dependent on?

• brain

• glucose

what happens to cortisol in a stress response

increased to produce more epinephrine

how does cortisol influence anti-inflammatory effects?

decreases the immune response

how does cortisol regulate blood pressure?

promotes heart and vasomotor effects

how does cortisol regulate metabolism?

influence glucose and energy production

What is the role of circadian rhythm in cortisol release?

Cortisol rises in the morning to prepare for the day.

what is the effect of cortisol on the liver?

increases gluconeogenesis

What is the effect of cortisol on adipose tissue?

Stimulates lipolysis and fatty acid mobilization

What is the effect of cortisol on skeletal muscle?

• increases proteolysis

• decreases glucose uptake

How does cortisol affect the pancreas?

Increases glucagon release.

What are the immune system effects of cortisol?

1. apoptosis of T-cells

2. decreased B-cell antibody production

3. decreased lymphocytes and eosinophils

How does cortisol influence blood pressure?

Increases responsiveness to catecholamines and vasomotor tone; can contribute to hypertension.

hyperadrenocorticism

hyperactivity of adrenal cortex leading to excess production of ONLY CORTISOL

what is another name for hyperadrenocorticism?

cushing’s disease

what is the therapeutic goal for hyperadrenocorticism?

reduce excessive production of cortisol in the adrenal cortex

what is the drug used to treat hyperadrenocorticism?

trilostane

why does excessive production of cortisol cause dermatological probles and what is an example?

• immunosupression

• calcinosis cutis

why does excessive production of cortisol cause hypertension?

increased sensitivity to catecholamines

why does excessive production of cortisol cause bilateral alopecia?

due to shortened anagen phase of hair follicle and premature catagen

why does excessive production of cortisol cause a pendulous abdomen?

• muscle atrophy of the abdominal muscles

• fat redistribution of adipose tissue

• hepatomegaly

why does excessive production of cortisol cause panting?

• mineralization of lung tissue

• muscle weakness

• pressure of distended abdomen on thorax

why does excessive production of cortisol cause polyruria?

• hyperglycemia

• glucosuria

• interference with ADH action

why does excessive production of cortisol cause polydipsia?

compensatory mechanism to polyuria

what metabolic process is induced from excess cortisol in adipose tissue?

lipolysis

what occurs to adipose tissue from excess cortisol?

release of fatty acids leading to fat redistribution

where is fat accumulation favored in the body during excess cortisol?

mesentery

why does excess cortisol cause weight loss?

induce lipolysis and proteolysis

how does excess cortisol lead to ulcers in the GI?

stimulates stomach acid secretion and reduces mucus production

what does excess cortisol do to appetite?

increases appetite

what triggers hepatomegaly due to excess cortisol

• lipolysis and fat mobilization

• GLYCOGEN synthesis and accumulation in the liver

what metabolic pathway is induced on muscles from excess cortisol?

proteolysis

how does excess cortisol influence bones?

1. decrease Ca2+ absorption from intestines

2. increase Ca2+ excretion through kidneys

3. skeletal mass decreases and bones are weaker

how does protein catabolism during excess cortisol affect the skin?

1. thin and inelastic skin

2. poor skin healing

3. poor scar formation

calcinosis cutis

accumulation of calcium in area of skin that is damaged from excess cortisol production

what can lead to hyperadrenocortism?

1. functional tumor

2. prolonged and excessive amounts of corticosteroids

how does excess cortisol influence collagen and fibroblasts of the skin?

• reduces collagen synthesis

• inhibits fibroblast proliferation

what hormone will accumulate in the liver due to excess cortisol?

glycogen

what is the mechanism of action for trolostane?

competitive inhibition of 3-beta0 hyroxysteroid dehydrogenase in the adrenal cortex

What are the 5 P's of canine Cushings syndrome?

Pendulous abdomen, Panting, Polyuria, Polydipsia, Polyphagia.

What causes hepatomegaly in cortisol excess?

Glycogen and fat accumulation in the liver.

Which liver process is upregulated by cortisol?

Gluconeogenesis.

Which hormone is the primary mineralocorticoid?

Aldosterone.