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Adrenal gland

Adrenal gland

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Adrenal gland. Anatomy. 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. Hormone secretion. Adrenal cortex - PowerPoint PPT Presentation

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Page 1: Adrenal gland

Adrenal gland

Page 2: Adrenal gland

Anatomy

Page 3: Adrenal gland

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

Page 4: Adrenal gland
Page 5: Adrenal gland

Hormone secretion

• Adrenal cortex– Steroid hormones

• Glucocorticoids• Mineralocorticoid• Androgens

• Adrenal medulla– Neurotransmitter

• Epinephrine• Norespinephrine

Page 6: Adrenal gland

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)

Page 7: Adrenal gland

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

Page 8: Adrenal gland
Page 9: Adrenal gland

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)

Page 10: Adrenal gland

• 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

Page 11: Adrenal gland
Page 12: Adrenal gland

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

Page 13: Adrenal gland

• Psychological stress– Acute stress

• Increased cortisol secretion

– Chronic stress• No alteration

– Depression• Increased cortisol production

Page 14: Adrenal gland
Page 15: Adrenal gland

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

Page 16: Adrenal gland
Page 17: Adrenal gland

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

Page 18: Adrenal gland

• 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

Page 19: Adrenal gland
Page 20: Adrenal gland

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)

Page 21: Adrenal gland
Page 22: Adrenal gland

• 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)

Page 23: Adrenal gland

• 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