Adrenal gland

1
Adrenal gland
2
Anatomy
3
Components

• Two compartments
• Adrenal Cortex (outer layer)
• Three layers
• Zona glomerulosa (15 )
• Zona fasciculata (75 )
• Zona reticularis (10 )
• Adrenal medulla (inner layer)
• Nerve tissue
• Highly developed vasculature

4
(No Transcript)
5
Hormone secretion

• Adrenal cortex
• Steroid hormones
• Glucocorticoids
• Mineralocorticoid
• Androgens
• Adrenal medulla
• Neurotransmitter
• Epinephrine
• Norespinephrine

6
Functional zonation

• Zona glomerulosa
• Mienralocorticoid secretion only
• No 17a-hydroxylase
• Tissue-specific expression of 11beta-hydroxylase
  (CYP11B2)
• Zona fasciculata
• Glucocorticoids production
• Difference in promoter that activates
  11beta-hydroxylase (CYP11B1)

7
Adrenal stroidogenesis

• Cholesterol
• LDL from circulation
• Receptor-mediated endocytosis
• Uptake regulated by StAR
• Regulated by cAMP
• Process
• Mostly identical to gonadal steroidogenesis
• Almost exclusively uses delta-4 pathway

8
(No Transcript)
9
Regulation of glucocorticoid secretion

• Role of hypothalamus-pituitary axis
• Hypothalamic CRF
• Stimulation of ACTH production by the anterior
  pituitary gland
• Increased secretion of POMC protein via increased
  transcription of mRNA
• ACTH
• Interacts with receptors in Zona facsiculata
• Increased cAMP production
• Increased steroidogenesis
• Increased IGF-II production (tissue growth)

10

• Glucocorticoids
• Negatively feedback to hypothalamus and anterior
  pituitary gland
• Inhibition of CRF and ACTH secretion
• Pattern of ACTH secretion
• Diurnal
• Circadian rhythm
• Pulsatile
• More frequent in men

11
(No Transcript)
12
Role of stress and immune system

• Proinflammatory cytokines
• Secreted during inflammation by immune cells
• IL-1, IL-6, and tumor necrosis factor alpha
• Increased ACTH secretion
• Direct stimulation of corticotroph
• Argumentation of CRF secretion
• Physical stress
• Increased CRF release
• CNS-mediated
• Normal counter-regulatory response

13

• Psychological stress
• Acute stress
• Increased cortisol secretion
• Chronic stress
• No alteration
• Depression
• Increased cortisol production

14
(No Transcript)
15
Glucocorticoids in circulation

• Over 90 exist as bound-form
• Alpha-globulin cortisol-binding globulin (CBG)
• Synthesized by the liver
• Very high affinity to cortisol
• Level affected by the estrogens () and
  glucocorticoids (-)
• Metabolized by the liver and kidney
• Converted to cortisone
• Reversible

16
(No Transcript)
17
Mechanism of action

• Receptors
• Intracellular/nuclear receptors
• Two variants (alpha and beta)
• GR-alpha
• Bound to heat-shock proteins (HSP 90 and 70)
• Dissociation after interacting with the hormone
• Activation of genes
• GR-beta
• Negative regulator of GR-alpha activity

18

• Mediation of anti-inflammatory response
• GR plus activator protein-1 (AP-1)
• Formation of Co-activator complex
• Allows transcription of genes without GRE
• Could be antagonistic
• Combination of GR with c-Jun or nuclear factor
  kappa B

19
(No Transcript)
20
Function of glucocorticoids

• Nutrient metabolism
• Increased hepatic gluconeogenesis
• Increased enzyme synthesis
• Inhibition of glucose uptake by the peripheral
  tissues
• Catabolic action
• Break-down of fats and muscles
• Serve as substrates for gluconeogenesis or source
  of energy
• Inhibits insulin action (diabetes)

21
(No Transcript)
22

• Stress response
• Maintenance of vasculature
• Synthesis of catecholamines
• Sympathoadrenal activity
• Stimulation of sympathetic nervous system
• Further stimulation of lipolysis
• Maintenance of body temperature (altered
  metabolism)

23

• Immune system
• Anti-inflammatory
• Prevention of lysozomal content leakage
• Prevention of leukocyte infiltration
• Atrophy of lymphatic system
• Decreased lymphocytes in circulation
• Regulation of IL-1beta production by activated
  monocytes
• Prevents over-stimulation of immune system