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Endocrinology > The glucocorticoids > Flashcards

The glucocorticoids Flashcards

1
Q

are synthesised in the

A

Zona fasiculata

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2
Q

all corticosteroids are synthesised from

A

cholesterol (27 c)

- enzymes work at 20/21 junction

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3
Q

the RLS of corticosteroid synthesis is catalysed by

A
  • sTAR
  • contains a C transfer domain (sTAR related transfer domain)
  • transport protein that regulates the uptake of cholesterol into the mitochondria
  • activity can be increased by ACTH / luteinising hormone (cAMP)
  • transported from outer MM to the inner MM
  • can enter the mitochondrion which contains P450scc enzymes
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4
Q

The actions of the enzyme P450scc include

A
  • activity increased by ACTH
  • 2 hydroxylase reactions produce 20,22 - dihydroxyC
  • final stage includes cleavage of bond between 20/22 to yield pregnenolone (21c)
  • 27cā€”- 21c
  • precursor for all other steroids
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5
Q

the regulation of P450scc

A
  • requires electrons for function
  • works in complex with 2 other proteins (andrenodoxin reductase and adrenodoxin)
  • these provide e-
  • always active but depends on supply of C
  • ACTH up regulates all of these genes that are part of the complex
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6
Q

all steroids will contain how many carbon atoms?

A

21

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7
Q

the inactive form of cortisol is referred to as

A
  • cortisone
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8
Q

CYP11B1 works by?

A

converting deoxycortisol to cortisol

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9
Q

cortisol is transported around the blood via?

A
  • hydrophillic
  • requires carrier proteins
  • 90% bound to transcortin
  • 10% to albumin
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10
Q

ACTH binds to which receptor?

A
  • melanocortin 2 receptor

- activates 2nd messenger cascades via cAMP

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11
Q

the effects of cAMP cascades on the adrenal cortex include

A
  • immediate actions, increased C transport into the M
  • subsequent, increased gene transcription of hydroxylases
  • increased LDLr

long term-
increased size and complexity of organelles (hypertrophy)
- increased number of cells (hyperplasia)

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12
Q

glucocorticoids bind to

A
  • GR
  • intracellular nuclear receptors
  • dimerise upon binding
  • translocate into the nucleus
  • bind to GRE present on DNA
  • increased protein synthesis
    of lipocortin (inhibits PLA2 pathway)- anti-inflammatory
  • immunosuppression
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13
Q

the main effects of cortisol is to

A
  • increase plasma glucose levels
  • inhibits glucose entry into tissues
  • increase hepatic glucneogenesis
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14
Q

metabolic effects of cortisol include

A
  • Protein - muscles - increased breakdown of protein - AA > wasting/ growth retardation.
  • Liver - increased uptake of AA - protein synthesis/ gluconeogenesis
  • Fat - increased mobilization of FA from adipose tissues - more gluconeogenesis/ redistribution from extremities to the central trunk areas
  • Cortisol- mobilizes fat and moves it into the central regions- evolution? Response to Long term stress
  • Electrolyte balance - large amounts= MC activity
  • Bones - reduced absorption of ca, enhanced excretion, inhibition of osteoblasts can lead to osteoporosis
  • CNS- mood/cognition
  • Immune system - reduce lymphocytes/ eosinophils , increase neutrophils, RBCs and platelets
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15
Q

Anti-inflammatory actions include

A
  • reduced leukocyte action
  • anti-allergic - inhibits histamine secretion and synthesis
  • immunosuppressive
  • anti-allergic medication (cortisol)
  • can treat RA
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16
Q

cushings syndrome is characterised by

A
  • XS cortisol levels
17
Q

cushings disease is caused by

A
  • pituitary tumour of corticotroph cells
  • elevated ACTH levels
  • negative feedback fails
  • hyperplasia of cortex
  • ectopic ACTH Producing tumor (lungs)
  • autonomous adrenal adenoma
18
Q

may be iatrogenic

A
  • caused by a dr
  • long term immunosuppression with synthetic cortisol analogues
  • shrinkage of adrenal gland - decreased ACTH (NEG FEEDBACK)
  • taken off these straight away can go into an adrenal crisis
19
Q

the treatment of cushings syndrome

A
  • surgery
  • radiotherapy to target cancer
    ]
  • metyrapone (11-Bhydroxyalase inhibitor)
  • Inhibits 11-deoxycortisol conversion to cortisol
20
Q

symptoms of Cushings syndrome include

A
  • central obesity
  • thin arms/legs
  • trunkal obesity
  • mobilisation of fat to central regions
  • muscle wastage
  • increased bone resorption
  • suppression of immune system
  • increased risk of infection
  • hypertension
  • elevated plasma glucose
  • suppression of glucose rendition capacity In kidney
21
Q

primary cause of hypo-adrenal function

A
  • Addisons disease

- 65% - autoimmune disease

22
Q

secondary cause of hypo-adrenal function

A
  • stopping long term glucocorticoid therapy

- or a disease of the pituitary gland (reduces ACTH)

Endocrinology (17 decks)

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