Testosterone Production: Leydig Cells and the HPG Regulatory Axis

Testosterone, the principal androgen in males, is synthesized primarily in the Leydig (interstitial) cells of the testes.

Biosynthetic Pathway

1. Cholesterol → (STAR protein) → inner mitochondrial membrane.
2. CYP11A1 (side‑chain cleavage) → pregnenolone.
3. CYP17A1 (17α‑hydroxylase/17,20‑lyase) → DHEA → androstenedione.
4. 17β‑HSD → testosterone.

Regulation (HPG Axis)

• Hypothalamus: GnRH pulse generator.
• Anterior pituitary: LH (stimulates Leydig cells) + FSH (supports Sertoli cells/spermatogenesis).
• Negative feedback: Testosterone (and estradiol via aromatization) inhibits GnRH/LH.
• Inhibin B (from Sertoli cells) selectively inhibits FSH.

Additional Sources

• Adrenal cortex (zona reticularis): DHEA, androstenedione (minor contribution; significant in females, adrenal pathology).
• Peripheral conversion: Androstenedione → testosterone in skin, liver, fat.

Clinical Correlates

• Primary hypogonadism: ↑ LH, ↓ T (testicular failure).
• Secondary hypogonadism: ↓/normal LH, ↓ T (pituitary/hypothalamic).
• Age‑related decline: ~1%/year after 30–40; not universal.

Leydig cells are the engine of male androgen production, tightly governed by the HPG axis.