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Human Body Study

Leydig Cells

The endocrine cells of the testis — the source of testosterone. They sit in the interstitial tissue between the seminiferous tubules, usually clustered around capillaries.

Named for the German anatomist Franz Leydig, who described them in 1850.

Schematic of the testis A labelled diagram of the testis. The left figure is a cut-away sagittal view showing the fibrous capsule (tunica albuginea), the septa dividing the testis into lobules, the coiled seminiferous tubules within each lobule, the mediastinum testis with its rete testis, the efferent ductules leaving the testis, the epididymis draped along its posterior border (head, body, tail), the vas deferens, and the spermatic cord with its testicular artery and pampiniform venous plexus. The centre figure is a magnified cross-section of a single seminiferous tubule with adjacent interstitium, showing tall Sertoli cells spanning the tubule wall, the spermatogenic lineage maturing from basement membrane to lumen, peritubular myoid cells, and Leydig cells in the interstitial space. The testis — cut-away and tubule cross-section scrotum mediastinum head body tail testicular artery pampiniform plexus vas deferens seminiferous tubule (cross-section) lumen capillary Scrotum & spermatic cord the skin sac that holds both testes outside the body,and the cord that suspends each testis carrying itsvessels, nerves, and vas deferens. Vasculature & nerves the testicular artery and the pampiniform venousplexus that cools it; lymphatics; autonomic nerves. Tunics & lobules the tough fibrous capsule (tunica albuginea), theserous outer tunica vaginalis, and the septa carvingthe testis into ~250 wedge-shaped lobules. Seminiferous tubules the tightly coiled tubes within each lobule wheresperm are made — about 250 m of tubule per testis. Intratesticular ducts straight tubules feed the rete testis (a networkin the mediastinum), which drains via efferentductules to the head of the epididymis. Sertoli cells tall nurse cells spanning the tubule wall;their tight junctions form the blood-testis barrier. Spermatogenic cells the germ-cell lineage, base to lumen — spermatogonia→ spermatocytes → spermatids → spermatozoa. Leydig cells endocrine cells between the tubules — thesource of testosterone, driven by LH. Interstitial tissue the loose stroma between tubules — capillaries,lymphatics, macrophages, and connective tissue. Left: sagittal cut-away of one testis with its epididymis and spermatic cord. Centre: magnified seminiferous tubule and adjacent interstitium. Not to scale.

Structure

Section titled “Structure”
  • Shape — large, polyhedral cells with abundant pink-staining (eosinophilic) cytoplasm.
  • Cytoplasm packed with smooth endoplasmic reticulum and mitochondria with tubulovesicular cristae — the hallmark of a steroid-hormone-secreting cell. Lipid droplets containing cholesterol esters (the substrate for testosterone) are common.
  • Reinke crystals — distinctive rod-shaped protein crystals seen in adult human Leydig cells (their function is unclear; useful as a diagnostic marker).
  • Position — cluster around capillaries, so secreted testosterone enters the bloodstream within seconds.

What they do

Section titled “What they do”
  • Make testosterone. The synthesis pathway is the standard steroidogenic route, in brief:
    1. LH (from the anterior pituitary) binds the LH receptor → Gs → cAMP → PKA.
    2. PKA activates StAR (steroidogenic acute regulatory protein), which shuttles cholesterol into the inner mitochondrial membrane.
    3. Cholesterol → pregnenolone by CYP11A1 (the rate-limiting cleavage step).
    4. Pregnenolone → progesterone → 17α-hydroxyprogesterone → androstenedione → testosterone through a series of cytochrome P450 and dehydrogenase enzymes shared with other steroidogenic tissues.
  • Make small amounts of other steroids — androstenedione, DHEA, and a little estradiol (via local aromatase).
  • Produce insulin-like 3 (INSL3) — a constitutive peptide hormone with a role in fetal testicular descent and, in adults, possibly bone metabolism.

Where the testosterone goes

Section titled “Where the testosterone goes”

Leydig cells supply two pools:

  • Systemic — testosterone diffusing into capillaries reaches the rest of the body, where it (or its conversion products dihydrotestosterone and estradiol) drives male physiology.
  • Intratesticular — testosterone diffuses into the seminiferous tubules, where it is held at extremely high local concentrations (~50–100× systemic blood levels) by Sertoli-cell androgen-binding protein. Spermatogenesis requires this local concentration; systemic testosterone alone is not enough.

This dual role is why exogenous testosterone shrinks the testes: external testosterone suppresses LH, Leydig cells switch off, intratesticular testosterone collapses, and spermatogenesis stalls — even though serum testosterone is high.

Regulation

Section titled “Regulation”

LH from the anterior pituitary is the only significant trophic signal. LH pulses follow GnRH pulses from the hypothalamus; see the HPG axis for the full loop, including the testosterone-driven negative feedback that closes it.

Three populations across life

Section titled “Three populations across life”

Although they all look broadly similar on histology, the Leydig cells active at different ages are actually distinct lineages:

  • Fetal Leydig cells — appear around week 8 of gestation, driven first by placental hCG (which acts on the LH receptor) and later by fetal pituitary LH. They produce the testosterone that masculinizes the bipotential embryo.
  • Neonatal Leydig cells — active during minipuberty in the first months of life, then largely regress.
  • Adult Leydig cells — a new population that arises during puberty under rising LH and produces adult-level testosterone for the rest of life.

The fetal/neonatal and adult populations are different cell lineages, not the same cells switched on and off. The adult population then declines slowly with age (~1% per year decrease in testosterone from the third decade onward), contributing to the gradual late-life fall in testosterone.

Key idea

Section titled “Key idea”

Leydig cells are the testis’s endocrine half. They convert an LH pulse into a testosterone pulse on a minute timescale, and that testosterone serves two completely different jobs: a systemic hormone for the rest of the body and a local paracrine signal that the neighbouring seminiferous tubule cannot do without.