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Adrenal gland

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

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Adrenal gland

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

  5. 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)

  6. 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

  7. 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)

  8. 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

  9. 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

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

  11. 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

  12. 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

  13. 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

  14. 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)

  15. 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)

  16. 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

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