Steroid Hormone Pathway

1. 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
2. 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
3. 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
4. Step 3: Sex Hormones from Androstenedione
   1. Androstenedione converted to Estrone or
   2. Androstenedione converted to Testosterone
      1. Testosterone converted to Estradiol
5. 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