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II. Physiology

  1. Cholesterol is precursor for 5 steroid hormone classes
    1. Progestagens (e.g. Progesterone)
    2. Glucocorticoids (e.g. Cortisol)
    3. Mineralcorticoids (e.g. Aldosterone)
    4. Androgens (e.g. Testosterone)
    5. Estrogens
  2. Synthesis sites
    1. Adrenal cortex: Glucocorticoids, Mineralcorticoids
    2. Women
      1. Corpus luteum: Progestagens
      2. Ovary: Estrogens
    3. Men
      1. Testis: Testosterone
  3. Conditions related to enzyme deficiencies
    1. Congenital Adrenal Hyperplasia
      1. 21-Hydroxylase deficiency is most common

III. Step 1: Steroid Synthesis – Cholesterol to Precursors

  1. Cholesterol converted to Pregnenolone
    1. Stimulated by ACTH release from anterior pituitary
    2. Key enzyme: Desmolase
  2. Pregnenolone converted to Progesterone
    1. Pregnenolone is precursor of all steroids
    2. Key enzyme: 3-B-Hydroxysteroid Dehydrogenase
  3. Progesterone converted to 17-a-hydroxyprogesterone
    1. Key enzyme: 17-Hydroxylase
    2. 17-a-hydroxyprogesterone is precursor
      1. Cortisol Synthesis (Go to step 2)
      2. Aldosterone Synthesis (Go to Step 4)
  4. 17-a-hydroxyprogesterone converted to Androstenedione
    1. Key enzyme: 3-B-Hydroxysteroid Dehydrogenase
    2. Androstenedione is sex hormone precursor (see Step 3)
      1. Estrone
      2. Testosterone
      3. Estradiol

IV. Step 2: Cortisol Synthesis from 17-a-hydroxyprogesterone

  1. 17-a-hydroxyprogesterone converted to 11-Deoxycortisol
    1. Key enzyme: 21-Hydroxylase
    2. Most common enzyme deficiency in steroid synthesis
      1. Congenital Adrenal Hyperplasia (with Virilization)
  2. 11-Deoxycortisol converted to Cortisol
    1. Key enzyme: 11-Hydroxylase
    2. Enzyme deficiency related condition
      1. Congenital Adrenal Hyperplasia (with Virilization)
  3. Cortisol

V. Step 3: Sex Hormones from Androstenedione

  1. Androstenedione converted to Estrone or
  2. Androstenedione converted to Testosterone
    1. Testosterone converted to Estradiol

VI. Step 4: Aldosterone from Progesterone

  1. Progesterone converted to 11-Deoxycorticosterone
    1. Key enzyme: 21-Hydroxylase
  2. 11-Deoxycorticosterone converted to Cortisosterone
    1. Key enzyme: 11-Hydroxylase
  3. Corticosterone converted to Aldosterone