C21 Steroids (21 carbon atoms)

• C21 steroids with an OH at position 17 are known as 17-hydroxysteroids. The only 17 OH steroid with hormonal activity is cortisol.
• The lipid-soluble 17 OH steroids are metabolized into water-soluble compounds before they are filtered and excreted in the urine.
• In the past, urinary 17 OH steroids were measured as an index of cortisol secretion. This has since been replaced by the measurement of the 24-hour urine-free cortisol.

C19 Steroids (19 carbon atoms)

• Adrenal Androgens:

  • These contain a keto group at position 17, hence they are called 17-ketosteroids.
  • They are conjugated with sulfate in the adrenal cortex, which makes them water-soluble. These water-soluble metabolites circulate in the bloodstream, are filtered by the kidneys, and excreted in the urine.

• The sulfated form is not produced in the gonads; thus, it's considered an index of androgen production by the adrenals.

• The major secreted form is dehydroepiandrosterone (DHEA).

• DHEA, DHEA sulfate, and androstenedione have very low androgenic activity. They primarily function as precursors for the conversion to the more potent testosterone and dihydrotestosterone (in both men and women).

• In adult males, excessive production of adrenal androgens has no clinical consequences. In prepubertal males, it causes premature penile enlargement and early development of secondary sexual characteristics. In women, excessive adrenal androgens cause hirsutism and virilization.

• Testosterone:

  • It's mainly produced by the Leydig cells of the testes.
  • The active hormone is lipid-soluble and not a 17-ketosteroid.
  • When metabolized, it's converted to a 17-ketosteroid and conjugated to become water soluble. In this form, it's filtered and excreted by the kidney.

• Urinary Excretion:

  • Urinary 17-ketosteroids are an index of all androgens, both adrenal and testicular.
  • In females and prepubertal males, urinary 17-ketosteroids are an index of adrenal androgen secretion.
  • In adult males (postpuberty), urinary 17-ketosteroids are 2/3 adrenal and 1/3 testicular, thus mainly an index of adrenal secretion.

  ---

  C18 steroids—estrogens (estradiol):

  • Aromatase converts androgen into estrogen.

  Regional synthesis

  • Each tissue contains only the pathways necessary to produce the hormones it typically secretes.

  • For instance, the zona glomerulosa only has the pathways of the first column because its main output is aldosterone.

  • The synthesis of all steroid hormones begins with the conversion of cholesterol to pregnenolone.

  • The enzyme that catalyzes this conversion is desmolase. This step controls the rate of all steroid hormone synthesis.

  • Synthesis in the zona glomerulosa:

    • Angiotensin II is the main stimulus to the zona glomerulosa, leading to the production of aldosterone, the major mineralocorticoid.

  • Synthesis in the zona fasciculata and the zona reticularis:

    • Normal hormonal output of the zona fasciculata and zona glomerulosa includes:
      • 11-Deoxycorticosterone: This weak mineralocorticoid is not significant under normal conditions. Almost all mineralocorticoid activity is due to aldosterone.
      • Corticosterone: also not significant under normal conditions. The majority of glucocorticoid activity is due to cortisol.
      • Cortisol: This is the main glucocorticoid secreted by the adrenal cortex, responsible for most of the hypothalamic and anterior pituitary negative feedback control of ACTH secretion.
    • Normal hormonal output of the zona reticularis includes:
      • Adrenal androgens: These weak, water-soluble androgens are significant secretions. However, they only produce masculinizing characteristics in women and prepubertal males when secretion is excessive.