Lecture 6 - peripheral endocrine glands

Question 1

Adrenal gland found

Answer 1

On top of both kidneys

Question 2

Question 3

Hormones produced by each zona of adrenal gland

Answer 3

Zona glomerulosa - Aldosterone ( mineral corticoid)
Zona fasciculata - Cortisol
Zona reticularis - androgens

Question 4

Sex hormones

Answer 4

Identical or similar to those produced by gonads
Most abundant and physiologically important is dehydroepiandosterone [(DHEA) male “sex” hormone]

Question 5

Adrenal glucocorticoids are

Answer 5

Steroid hormones

Question 6

Adrenal cortex hormones characteristics

Answer 6

Lipophilic
- diffuse through plasma membrane

Rate of secretion is controlled by rate of synthesis
- Carried in blood by plasma proteins
> Cortisol- corticosteroid-binding globulin (transcortin)
> Aldosterone & DHEA – albumin

Bind to specific receptors in target cell cytoplasm
- Mineralcorticoids: mineralcorticoid receptor (MR)
- Glucocorticoids: glucocorticoid receptor (GR)
- DHEA: androgen receptor (AR)

Hormone-receptor complex move to nucleus and binds to complementary hormone-response element in DNA
- mineralcorticoid response element
- glucocorticoid response element
- androgen response element

Binding leads to specific gene transcription, synthesis of proteins – carry out the effects of hormone

Question 7

What is aldosterone and how is it regulated?

Answer 7

Mineral corticoids
RAAS (renin-angiotensin-aldosterone system)
- all other adrenal hormones regulated by hypothalamus-pituitary axis

Question 8

Mineral corticoids: ESSENTIAL FOR LIFERAAS (renin-angiotensin-aldosterone system)

Answer 8

NB!!!
Angiotensin II binds to zona glomerulosa to prod aldosterone

Juxtaglomerular complex in kidneys detect a change in [ion] and respond by secreting renin

Question 9

Regulation of aldosterone secretion is largely independent

Answer 9

of anterior pituitary control

Question 10

Adrenal Glands: Cortisol

Answer 10

Metabolic effects: Important role in carbohydrate, protein and fat metabolism
Executes significant permissive actions for other hormones (catecholamines to induce vasoconstriction and effects on heart)
Resist stress
Metabolic effects:
Stimulates hepatic gluconeogenesis (amino acids  glucose) to replenish glycogen stores (between meals and during fasting, glycogen (stored glucose) in liver becomes depleted as it is broken down to release glucose in blood) – maintain normal blood glucose levels between meals
Inhibits glucose uptake and use by many tissues, but not the brain
Stimulates protein degradation in many tissues, especially muscle (amino acids available for gluconeogenesis)
Facilitates lipolysis (breakdown of lipid in adipose tissue, releasing free fatty acids in blood)

Question 11

Question 12

Adrenal Glands (zona reticularis)

Answer 12

Secretes both male and female sex hormones in both sexes

Dehydroepiandrosterone (DHEA)
Only adrenal sex hormone that has any biological importance
Overpowered by testicular testosterone in males

Physiologically significant in females where it governs
Growth of pubic and axillary hair
Enhancement of pubertal growth spurt
Development and maintenance of female sex drive

Question 13

DHEA

Answer 13

ACTH control DHEA output – negative feedback outside HPA axis – inhibits gonadotropin releasing hormone

Cortisol and DHEA output not always similar, marked surge in DHEA output at puberty; cortisol remains the same

Surge in DHEA begins at puberty, peaks between 25 and 30, tapers off after 30 and at 60 plasma [ ] is less than 15% of peak level

DHEA replacement therapy: increase in lean muscle mass and decrease in fat, increase in psychological well being and improved ability to cope with stress

Women taking DHEA: increase facial hair, ovarian and breast cancer risk, reduction in HDL

Question 14

Disorders of Adrenocortical Function
Aldosterone hypersecretion

Answer 14

May be caused by
Hypersecreting adrenal tumor made up of aldosterone-secreting cells
Primary hyperaldosteronism or Conn’s syndrome
Inappropriately high activity of the renin-angiotensin system
Secondary hyperaldosteronism

Symptoms
Excessive Na+ retention (hypernatremia) and K+ depletion (hypokalemia)
High blood pressure due to excessive Na+ and fluid retention

Question 15

Cortisol hypersecretion
Cushing’s syndrome/disease

Answer 15

Causes
Overstimulation of adrenal cortex by excessive amounts ACTH due to pituitary adenoma (Cushing’s disease)
Adrenal tumors that uncontrollably secrete cortisol independent of ACTH
ACTH-secreting tumors located in places other than the pituitary
iatrogenic
Signs and symptoms
Hyperglycemia and glucosuria (adrenal diabetes)
Abnormal fat distributions (lipodystrophy)
“buffalo hump” and “moon face”

Question 16

Question 17

Question 18

Cushing’s syndrome

Answer 18

Excess gluconeogenesis-hyperglycemia (mimicks diabetes)
Muscle protein breakdown and lipolysis – wasting
Deposits extra fat in trunk and face – increased appetite and food intake
Classical appearance: thin arms & legs; moon face; plump cheeks
CNS – initial mood elevation followed by depression; difficulty with learning and memory

Question 19

You are walking in the wilderness and encounter a rhino which chases you up a tree. Is your stress response mediated by cortisol?

Answer 19

No, adrenaline and noradrenalin

Question 20

The illegal use of anabolic steroids by bodybuilders and athletes periodically receives much attention. Do these illegal steroids include cortisol?

Answer 20

No, has opposite effects:
breaks down muscle, increases blood glucose

Question 21

Disorders of Adrenocortical Function
Adrenal androgen hypersecretion

Answer 21

Adrenogenital syndrome
Symptoms:
Adult females
Hirsutism (woman who develop a male pattern of body hair)
Deepening of voice, more muscular arms and legs (virilization)
Breasts become smaller and menstruation may cease

Newborn females
Have male-type external genitalia (female pseudohermaphroditism)

Prepubertal males
Develop male secondary sexual characteristics prematurely, e.g. deep voice, beard, enlarge penis, sex drive
Precocious pseudopuberty (vroeë pseudo-puberteit)

Adult males
Has no apparent effect

Question 22

Question 23

Disorders of Adrenocortical Function
Adrenocortical insufficiency

Answer 23

Primary adrenocortical insufficiency
= Addison’s disease
- Autoimmune disease: destruction of adrenal cortex by erroneous production of attacking antibodies

Aldosterone deficiency:
Hyperkalemia (disturbs cardiac rhythm) and hyponatremia (reduces ECF volume, blood volume – lowers blood pressure: hypotension)

Cortisol deficiency:
Poor response to stress
Hypoglycemia
Lack of permissive action for many metabolic activities
Hyperpigmentation: - cortisol -> +ACTH (alpha-MSH and ACTH are both cleaved from the same pro-opiomelanocortin precursor)

Secondary adrenocortical insufficiency
Occurs because of pituitary or hypothalamic abnormality

Question 24

Would someone with Addison’s disease have normal, low or high levels of ACTH in the blood?

Answer 24

high levels of ACTH and CRH (negative feedback)

Question 25

Cortisol

Answer 25

Stress hormone – long term stress
Epinephrine – rapid stress response
Protective effect against HYPOGLYCAEMIA
PERMISSIVE EFFECT
Permissive to glucagon and catecholamines

Question 26

Question 27

Cortisol functions

Answer 27

Promotes gluconeogenesis in the liver
Amino acids –> glucose –> +[blood glucose]

Causes breakdown of skeletal muscle proteins
Provide substrate for gluconeogenesis

Enhances lipolysis
Fatty acids are available to peripheral tissue for energy

Suppresses the immune system

Causes negative calcium balance (induce osteoporosis)
- intestinal Ca2+ absorption; + renal Ca2+ excretion
Catabolic to bone tissue

Influences brain function
Mood changes; memory and learning alterations

Question 28

Cortisol: Therapeutic Drug

Answer 28

Suppresses the immune system
Preventing cytokine release & antibody production by WBCs

Inhibits the inflammatory response
Decreasing leukocyte mobility & migration

Used to treat
Bee stings, poison ivy, and pollen allergies
Prevents rejection of transplanted organs
BUT: serious side effects
Nonsteroidal anti-inflammatory drugs (NSAIDs), eg. ibuprofen