Steroid Hormone Pathway

Aka: Steroid Hormone Pathway, Sex Hormone Synthesis, Cortisol Synthesis, Aldosterone Synthesis

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II. Physiology: General

  1. Images
    1. AdrenalFunction.png
  2. 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
  3. Synthesis sites
    1. Adrenal Cortex: Glucocorticoids, Mineralcorticoids
    2. Women
      1. Corpus luteum: Progestagens
      2. Ovary: Estrogens
    3. Men
      1. Testis: Testosterone

III. Physiology: Step 1 (Steroid Synthesis - Cholesterol to Precursors)

  1. Cholesterol converted to Pregnenolone
    1. Stimulated by ACTH release from anterior pituitary
    2. Key enzyme: Desmolase (Cholesterol side chain cleavage enzyme)
    3. Inhibitors: Aminoglutethimide (Aromatase Inhibitor), Mitotane, Ketoconazole
  2. Pregnenolone converted to Progesterone
    1. Pregnenolone is precursor of all steroids
    2. Key enzyme: 3-B-Hydroxysteroid Dehydrogenase
    3. Inhibitors: Mitotane
  3. Progesterone converted to 17-a-hydroxyprogesterone
    1. Key enzyme: 17-Hydroxylase
    2. Inhibitors: Abiraterone acetate (Zytiga), Etomidate, Ketoconazole
    3. 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. Physiology: 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: 11B-Hydroxylase
    2. Inhibitors: Etomidate, Ketoconazole, Metyrapone, Mitotane
    3. Enzyme deficiency related condition
      1. Congenital Adrenal Hyperplasia (with Virilization)

V. Physiology: Step 3 (Sex Hormones)

  1. DHEA to Testosterone or Estradiol
    1. Enzyme: 17B-Hydroxysteroid Dehydrogenase
  2. Testosterone to Dihydrotestosterone (DHT)
    1. Enzyme: 5a Reductase
    2. Inhibitors: 5a-Reductase Inhibitor (e.g. Finasteride)
  3. Estrogens from Androstenedione
    1. Androstenedione converted to Estrone or
    2. Androstenedione converted to Testosterone
      1. Testosterone converted to Estradiol

VI. Physiology: 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
    1. Key enzyme: Aldosterone synthase
    2. Inhibitors: Metyrapone, Mitotane
  4. Aldosterone
    1. See Sodium and Water Homeostasis

VII. Pathophysiology

  1. Aldosterone
    1. Hyperaldosteronism
  2. Cortisol
    1. Addison's Disease (Adrenal Insufficiency)
    2. Cushings Disease
  3. Androgens
    1. Congenital Adrenal Hyperplasia
      1. 21-Hydroxylase deficiency is most common
  4. Epinephrine and Norepinephrine (Adrenal Medulla)
    1. Pheochromocytoma

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