Section 4-adrenal gland Flashcards Preview

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Flashcards in Section 4-adrenal gland Deck (93)
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1

Describe adrenal glands: their name, weight, place

v Paired glands v weight of 8-10 g v situated above and medial to the kidneys

2

What is the structure of adrenal glands

  • surrounded by fibrous capsule and adrenal divided into functional layers
  •  cortex is about 90 % of adrenal mass, inner medulla about 10 %
  •  cortex has 3 zones: Zona f. is thickest (about 75 % of cortex) there is cortex and medulla, 
  • In the order from outside to inside
  1. capsule
  2. zona glomerulosa
  3. zona fasciculata
  4. zona reticularis
  5. adrenal medulla

3

which part of the adrenal gland secrete what hormone

4

for all hormones synthesized in medulla what is the common precursor

cholesterol->pregnenolone

5

what is the common enzyme thant converts cholesterol into pregnelone

p450scc

On inner mitochondrial membrane, P450scc (side-chain cleavase) betwen carbon 17 and 20 cleaves the
side chain of cholesterol to produce pregnenolone

6

what specific enzymes are synthesized only by the cells producing cortisol, aldosterone, androstenedione

cortisol- p450c17

aldosterone-aldosterone synthase

androstenedione- 17,20 lyase

7

sources of cholesterol

Main source is the diet, but
can also be synthesized from acetyl-CoA

8

what determines what steroid is synthesized in a cell or tissue

Cell specific expression of enzymes determines what
steroid is produced in a cell or tissue

9

where enzymes in sterod producing cells are located

vSome enzymes are in the mitochondria others in the
endoplasmic reticulum. Steroid intermediates shuttle
back and forth

When steroid is being synthesized, steroid metabolites needs to shuttle between these organelles

10

How steroids are different from each other

vMost steroids differ by minor modifications of side
groups, often hydroxyl groups

11

How intitation of steroidogensis happen and describe this process ( by which protein is regulated, where happens)

  • The first step common toall steroids is the formationof pregnenolone from cholesterol
  • Takes place in the mitochondria
  • Uptake of cholesterol is a rate limiting step and
  • Regulated by StAR protein (Steroid Acute Regulatory

protein)

  • On inner mitochondrial membrane, P450scc (side-chain cleavase) cleaves the side chain of cholesterol to produce pregnenolone

12

How StAR is regulated 

StAR is cAMP-inducible gene and increases in response to tropic hormones
(i.e. ACTH in the adrenal gland and gonadotropins in gonads

When cAMP is increased, STAR concentrations increase, any protein hormone that can increase cAMP

13

Is cortisol stored?

No

14

Half life of cortisol is

70-120 min

15

what happens to cortisol after 70-120 minutes

  • Converted to inactive

cortisone and other
metabolites by liver (for
excretion in urine) and by
other target cells

  • In some cells, cortisone can

be reconverted to cortisol

16

How cortisol secretion is regulated

17

Function of cortisol (brain, CHO, adipose, skin, GI, growth)

Multiple functions depending on cell type

  1. brain
  • depression
  • psychosis

     2. carbohydrate metabolism 

  • increased hepatic glycogen deposition
  • increased peripheral insulin resistance
  • increased gluconeogenesis (promotes protein catabolism)
  • increased free fatty acid production
  • overall diabetogenic effect ( more glucose is circulating, but not uptaken and protein breakdown)

    3. GI

  • peptic ulcerations

   4.Growth and developement

  • Decreased linear growth

   5. Skin

  • skin thinning
  • muscle atrophy

   6. Adipose

  • promotes visceral obesity

18

on what hormones cortisol has an effect

Decreasaed LH, FSH, TSH release

Decreased GH secretion

19

How cells save themselves from prolonged action of cortisol

Type 2 11 beta HSD

converts cortisol to cortisone ( more water soluble) can be excreted in kidneys

20

Why cortisol/cortisone conversion is important in relation to aldosterone

  • Cortisol can activate the aldosterone receptor
  • vThe plasma concentrations of cortisol are about 100-1000 fold higher than the concentration of aldosterone
  • Aldosterone responsive cells therefore have to inactivate cortisol in order to respond specifically to aldosterone

 

21

Enzyme deficiency of HSD 11 beta 2 can lead to

vEnzyme deficiency of HSD11B2 → “AME” syndrome
(apparent mineralocorticoid excess)
vAt high concentrations cortisol interacts with MR
leading to Aldosterone- like symptoms

when there is high cortisol , it can act as aldosterone, causing problems

22

why there are hydrocortisone in creams

Hydrocortisone creams are used on the skin to treat swelling, itching and irritation. They can help with skin problems such as:

eczema

Skin has HSD1, so can convert back to cortisol

23

where cortisone can be converted back to cortisol , where does it go and what can happen if there is an overload of cortisol

kidney and other cell types inactivate cortisol to prevent inappropriate
activation of the aldosterone receptor – when cortisol levels are too
high HSD2 is
v overwhelmed and cortisol stimulates Na+/K+ exchange in kidney
causing
v hypokalemia and hypertension

24

How bicohemically cortisol acts on cells

Acts by increasing transcription of specific genes via activating a
cytoplasmic transcription factor (Class I receptor i.e. cytosolic)

needs to dimerize to be active

25

Effects of cortisol are generally opposite to 

Effects are generally opposite to insulin and similar to GH (i.e.
increase in blood glucose) at the expense of protein and fat. Action
depends on the target cells

increased catabolsim in muscles, adipocytes and lymphocytes and increased synthesis of glycogen and gluconeogenesis

26

What effect cortisol has on liver 

vOverall: Anabolic
effect in the liver


vIncrease of blood
glucose despite the
increase in
glycogen storage

27

How cortisol can be used as an anti-inflammatory drug and what aree the consequences

  • Cortisol inhibits the immune response and hence is antiinflammatory
  • Widely used to treat inflammatory conditions (i.e. rheumatoid arthritis and other immune disorders)
  • Leads to atrophy of the lymph nodes and thymus (activation of apoptosis)
  •  Decrease in number of lymphocytes and antibody production
  • Patients become susceptible to infections
  • Cortisol acts by the same dimer system and acts on antibody transcription

28

How cortisol modulates other hormone action

v Sensitizes arterioles to the action of norepinephrine
(hypertension)

v Permissive effect on the action of norepinephrine on
carbohydrate metabolism (glycogenolysis →
hyperglycemia)

29

How cortisol can act on CNS

Apart from depression, it can increase activity of CNS leading to euphoria

30

Can cortisol act as other hormones

v Can act as a mineralocorticoid (increase of extracellular
fluid) because it interacts with the mineralocorticoid
receptor.