Adrenal glands

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Adrenal glands

• Located adjacent to upper surface of each kidney
• Comprised of steroidogenic and chromaffin tissue
• Chromaffin tissue present in medulla
• Steroidogenic tissue forms cortex
• In some species, the tissues are intermingled
• Vascularized by arterial branches from the
  abdominal aorta
• Venous flow connects to inferior vena cava (often
  via the renal vein)

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Chromaffin tissue

• component of the autonomic nervous system
• sympathoadrenal system gt contributes to stress
  response
• Products epinephrine (80) norepinephrine
  (20)
• Epinephrine adrenaline

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Chromaffin cells

• Each cell innervated by a cholinergic,
  preganglionic sympathetic neuron
• Acetycholine gt depolarization and release of
  catecholamines
• Enkephalins (met- and leu-) are co-packaged,
  co-released with catecholamines
• Morphine and met-enkephalin activate same
  receptors
• Analgesia? Runners high?

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Physiological effects of catecholamines

• Prepares body for fight or flight
• Depresses activity within GI tract
• Force, rate of heartbeat increase
• Increased bloodflow to muscles, brain, coronary
  arteries
• Reduced bloodflow to skin, digestive tract,
  kidneys
• Adrenaline promotes glycogenolysis
• Noradrenaline promotes lipolysis
• Net effect elevation of blood glucose levels

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Adrenal Cortex

• Three morphologically, functionally distinct
  layers
• Zona glomerulosa (outer)
• Zona fasciculata (middle)
• Zona reticularis (inner)
• Fetal adrenal cortex (source of androgens for
  placental estrogen production)
• X zone

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Function of zones of adrenal cortex

• Zona glomerulosa produces mineralocorticoids
• Aldosterone gt promotes Na reabsorption in kidney
• 11-deoxycorticosterone
• Zona fasciculata produces glucocorticoids
• Cortisol (hydrocortisone)
• corticosterone
• Zona reticularis produces androgens
• testosterone
• Hormonal products are synthesized from
  cholesterol (steroid hormones)

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Adrenal hormone synthesis

• Cholesterol is obtained from circulating LDLs
• LDLs are major cholesterol transport complexes
• LDLs have inner hydrophobic core (cholesterol,
  triglycerides)
• Outer, polar layer surrounds core
• Phospholipids
• apolipoproteins

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Adrenal hormone synthesis, contd.

• Apolipoproteins bind to LDL receptors on adrenal
  cells
• Adrenals, ovarian corpus luteum have greatest
  of LDL binding sites
• Stimulates endocytosis (enhanced by ACTH)
• LDLs catabolized in lysosomes
• Cholesterol is modified by a series of
  hydroxylation reactions
• Enzymes involved cytochrome P450 superfamily
• Enzymes present in mitochondria, endoplasmic
  reticulum

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Glucocorticoid production

• Regulated by pituitary ACTH
• ACTH stimulated by CRF from brain
• Negative feedback regulates stress axis
• Cortisol inhibits CRF
• ACTH activates 7 transmembrane domain receptor gt
  cAMP pathway
• Stimulates P450scc mRNA expression
• ACTH also stimulates IGF-II production
• May mediate trophic effects of ACTH

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Glucocorticoids Physiological roles

• Mediates stress responses within the body
• Opposes insulins actions
• Increases synthesis of gluconeogenic enzymes
• Enhances lipolysis in fat cells (by preventing
  glucose uptake)
• Can cause proteolysis in muscle cells
• Allows proper functioning of sympathoadrenal
  system
• Necessary for catecholamine synthesis and
  reuptake
• May prevent degradation by COMT

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GlucocorticoidsPhysiological roles

• Parturition and sheep studies
• Corticosterone levels increase in fetal sheep
  several days prior to birth
• Infusions of ACTH induce premature birth
• Required (along with prolactin) for lactogenesis
  in the mouse
• Anti-inflammatory and immunosuppressive actions

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Renin-angiotensin system

• Regulates aldosterone production by zona
  glomerulosa
• Renin is secreted by juxtaglomerular (jg) cells
  of nephrons
• Jg cells replace smooth muscle cells of arteriole
  prior to its entry into malpighian corpuscle
• Release controlled by
• decrease in plasma fluid volume
• sympathetic nervous system
• Na flux across distal tubules

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Renin-angiotensin system

• Renin is proteolytic enzyme
• splits leucine-valine bond in angiotensinogen
  (produced in liver)
• Yields decapeptide angiotensin I (biol. inactive)
• Converted to angiotensin II in several tissues
  (e.g., lung)

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Angiotensin II

• Angio II is potent pressor substance
• Causes contraction of vascular smooth muscle
• Stimulates aldosterone production by zona
  glomerulosa

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Aldosterone actions

• Acts on distal tubules possibly collecting
  ducts
• Activates cation exchange mechanism (Na taken
  in, K or H extruded)
• Receptor is hormone-dependent transcription
  factor
• Receptor binds aldosterone and cortisol with
  equal affinity
• target cells of aldosterone protected by 11 beta
  hydroxysteroid dehydrogenase
• Converts cortisol or corticosterone to cortisone

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Aldosterone regulation

• Primarily controlled by angio II
• ACTH can stimulate
• Low K inhibits aldosterone secretion
• Increased Na reabsorption exerts negative
  feedback (via JG cell renin production)

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Glucocorticoid receptors

• Hormone-dependent transcription factors
• Associate as dimers
• Activate / repress genes

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Group discussion

• Addisons disease
• Define primary, secondary causes
• Physical symptoms
• Explain physiological basis for hypotension
• Cushings disease
• Define primary, secondary causes
• Explain physiological basis of the following
  symptoms glucose intolerance, hirsutism,
  polyuria, polydipsia
• 17 hydroxylase deficiency
• Phenotype
• Physiological basis of disease
• treatment

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Addisons disease

• Primary
• Atrophy due to autoimmune disease or tuberculosis
• Idiopathic atrophy (cortex only)
• Secondary or tertiary
• Pituitary or hypothalamic origin
• Symptoms
• Weakness, pigmentation of skin, weight loss,
  hypotension, salt craving, hypoglycemia, loss of
  body hair

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Addisons, contd.

• Weight loss, vomiting are often initial symptoms
• Often misdiagnosed as eating disorder
• Severe hypotension can result gt collapse
• Hypotension with hyperpigmentation are hallmarks
  of disease

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Cushings disease

• Due to prolonged or excess secretion of
  glucocorticoids
• Origins primary (adrenal tumors), secondary
  (adrenal hyperplasia due to excess ACTH)
• Central obesity, hypertension, glucose
  intolerance, hirsutism, thinning of muscles in
  extremities, osteoporosis (loss of protein
  matrix), polyuria, polydipsia (solvent drag due
  to excess glucose)