Biochemistry Objectives 49

1.Etiologies of six CAH steroidogenesis cases:

  1. StAR deficiency: causes sexual infantilism and salt loss due to the inability to produce any steroid hormones
  2. 3OH-SD (5,4-isomerase): causes mild virilism (due to DHEA shunt) and salt loss due to the inability to produce DOC or aldosterone
  3. 21-hydroxylase: causes virilism (due to testosterone shunt) and salt loss due to the inability to produce DOC or aldosterone
  4. 11-hydroxylase: causes virilism and hypertension due to high levels of DOC without aldosterone
  5. 18-hydroxylase: causes an initial salt loss followed by hypertension due to increased DOC and testosterone
  6. 17-hydroxylase: causes hypertension but no salt loss due to the cortisol pathway production of DOC.

2.Aldosterone action on Na+ retention and K+ secretion: aldosterone induces DGK to open apical renal distal convoluted tubule Na+ channels (permease hypothesis), increases basolateral Na+/K+ pumps (Na+ pump hypothesis), and increases mitochondrial activity to increase Na+/K+ pump use (metabolic hypothesis).

3.Renin and ACE in angiotensin II formation: renin catalyzes the conversion of angiotensinogen to angiotensin I, while ACE converts angiotensin I to angiotensin II

Degradation of angiotensin II via angiotensin III: angiotensin II is converted to angiotensin III via aminopeptidase, and angiotensin III is broken down by angiotensinases to make inactive products

4.Aldosterone mechanisms in:

  1. Autosomal recessive type I pseudohypoaldosteronism: mutation in the downstream protein signaling after aldosterone binds MR
  2. Autosomal dominant type I pseudohypoaldosteronism: mutation in the mineralocorticoid receptor causing an inability to bind aldosterone
  3. Conn’s syndrome (primary hyperaldosteronism): small adenoma in the adrenal zona glomerulosa causing an increase in aldosterone
  4. Liddle syndrome (inherited pseudohyperaldosteronism): mutation in the epithelial Na+ channel causing an increase of sodium mimicking the effect of aldosterone
  5. Licorice consumption (acquired pseudohyperaldosteronism): licorice consumption blocks 11-hydroxysteroid dehydrogenase, thus blocking cortisol degradation. Cortisol can then act as aldosterone (since it binds to the aldosterone receptor efficiently) and increases Na+ reabsorption.

5.Control of ANP secretion: ANP secretion is controlled by 1 (excitatory) and 1 (inhibitory) adrenergic receptor binding to catecholamines

ANP action in the CNS: ANP decreases drinking and salt appetites, is a vasodilator, and decreases aldosterone release

Action as an emergency hormone to counteract high salt intake: high salt take increases blood pressure, and expands the atrial walls. ANP is released to lower blood pressure, and acts as an emergency hormone to bring blood pressure back to normal.

6.Blood pressure lowering:

  1. Captopril: an ACE inhibitor; blocks conversion of Ang I to Ang II
  2. Sartans: blocks Ang II receptors so that Ang II loses its vasoconstrictive property
  3. Spironolactone: aldosterone receptor antagonist causes decreased Na+ reabsorption to lower blood pressure in the face of high hormone levels
  4. ANP: opposes angiotensin, and increases aldosterone release while lowering renin levels

7.Biosynthesis of aldosterone and the effects of:

  1. Angiotensin II: angiotensin II upregulates aldosterone to increase blood pressure
  2. ANP: ANP downregulates aldosterone to decrease blood pressure