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• Adrenal androgens

  • Masculinizing effects
  • Promote protein anabolism and growth

  
• Testosterone

  The most active androgen
• DHEA and androstenedione

  Have less than 20% testosterone activity
• Effects of adrenal androgen secretion rate

  • Normal secretion exerts very little masculinizing effects
  • Excessive secretion produces appreciable masculinization

  
• Effects of excess adrenal androgens

  1. In adult male: just expressing the existing characteristics

  2. In prepubertal boys: can cause precocious (early) development of the secondary sex characteristics without testicular growth

  
• Adrenal estrogen

  • Androstenedione is converted in fat and other peripheral tissues into testosterone and estrogens (aromatization)
  • This represents an important source of estrogen in men and postmenopausal women

  
• Mechanism of action of glucocorticoids

  1. GC receptor: Nuclear

  2. GC-GCR complex act as transcription factor of certain genes

  
• Stress

  • Any change in the environment that changes or threatens to change an existing optimal steady state
  • Stress activates processes at the molecular, cellular, or systemic level to restore the previous homeostatic reactions
  • Some stresses stimulate ACTH secretion
  • Most stress stimulate both ACTH and sympathetic nervous system

  
• Function of circulating glucocorticoids


  • May be maintenance of vascular reactivity to catecholamines
  • Short term increase in ACTH is beneficial
  • Long term increase in ACTH is harmful and disruptive causing Cushing syndrome and other abnormalities

  
• Role of ACTH in glucocorticoid secretion


  • Basal glucocorticoid secretion and glucocorticoid secretion in stress depend on ACTH from pituitary
  • Half-life: 10min in blood
  • Adrenal responsiveness: increases the sensitivity of adrenal to subsequent doses of ACTH
  • Pattern of ACTH secretion: Irregular bursts, Most frequent in early morning, Least frequent in evening
  • In adrenal insufficiency: Diurnal (circadian) rhythm in ACTH secretion is present in patients receiving constant doses of GCs
  • Negative feedback: Free glucocorticoids inhibit ACTH secretion at pituitary and hypothalamic levels, Degree of inhibition proportional to glucocorticoid plasma level, Drop in resting glucocorticoid levels stimulates ACTH secretion, In adrenal insufficiency: ACTH secretion rate markedly increase (absence of -ve feedback)

  
• Aldosterone action

  • Na+ retention (from urine, saliva, sweat, colon), Expands ECF volume, K+ excretion (Kaluresis; K diuresis), H+ excretion (acidic urine)
  • Renal site of action: Principles cells (P cells) of the collecting ducts
  • Mechanism of action: Receptors (MR) in the cytoplasm, Aldosterone-MR complex move to the nucleus and cause gene transcription, Increase ENaC insertion into the cell membrane from a cytoplasmic pool (Increase ENaC activity), Increase synthesis of ENaC

  
• Factors in the regulation of Na+ excretion

  • Aldosterone, GFR, Atrial natriuretic peptide (ANP), Presence or absence of osmotic diuresis, Change in tubular reabsorption of Na+ independent of aldosterone