Physiology · Reproduction, pregnancy and the fetus

The male gonadal axis and spermatogenesis !

Regulation
Exam priority: high

The brain sends pulsed signals to the testes, which make testosterone and, over about two and a half months, new sperm.

Updated 2026-11-01

Also called: Hypothalamic–pituitary–testicular axis, HPG axis (male)

See it in 3D: Testes · Epididymis · Pituitary gland · Hypothalamus · Seminal vesicles · Ductus deferens

What it is

Pulsed GnRH from the hypothalamus drives LH and FSH from the anterior pituitary. LH acts on Leydig cells to make testosterone; FSH acts on Sertoli cells, which nurse developing sperm inside the seminiferous tubules. Testosterone and inhibin B feed back to keep the system steady. The lab pattern of LH, FSH and testosterone tells you where a fault lies.

How it works, step by step

Hypothalamic neurons, triggered by kisspeptin, release GnRH in pulses into the portal blood of the pituitary stalk.
Each GnRH pulse makes gonadotrophs release LH and FSH into the systemic circulation.
LH binds Leydig cells in the interstitium and activates cholesterol side-chain cleavage, the rate-limiting step to testosterone.
FSH binds Sertoli cells, which form the blood–testis barrier and secrete androgen-binding protein that keeps testosterone high in the tubule.
Spermatogonia divide by mitosis, enter meiosis as primary spermatocytes and become haploid spermatids.
Spermiogenesis remodels spermatids into spermatozoa (acrosome, condensed nucleus, flagellum); the whole cycle takes about 64–74 days.
Sperm gain motility and fertilizing ability while passing through the epididymis over roughly 1–2 weeks.
Testosterone feeds back on hypothalamus and pituitary (partly after aromatization to estradiol); inhibin B selectively lowers FSH.

Hormone axes and feedback

Hypothalamic–pituitary–testicular axisLesion None (normal)

Tap a box to see the hormone, or choose a lesion to see the lab pattern.

Stimulates (+)
Inhibits / negative feedback (−)
Level ↑
Level ↓

Tap Leydig or Sertoli cells, then choose a lesion to see the lab pattern of each hypogonadism.

Reference values (adult)

Parameter	Value	Note
Total testosterone (morning)	≈300–1000 ng/dL	laboratory ranges vary; lowest in the evening
Duration of spermatogenesis	≈64–74 days	a change in fertility shows up about 3 months later
Semen volume	≥1.4–1.5 mL	WHO lower reference limits (2010–2021)
Sperm concentration	≥15–16 million/mL	WHO lower reference limits (2010–2021)
Scrotal temperature	≈2–3 °C below core	pampiniform plexus countercurrent cooling

Approximate values for a healthy adult at rest; each laboratory sets its own ranges.

Regulation

+Kisspeptin and pulsatile GnRH: Release LH and FSH; pulses start the axis at puberty.
−Testosterone (and estradiol made from it): Lowers GnRH pulse frequency and LH release.
−Inhibin B (Sertoli cells): Lowers FSH only.
−Prolactin, stress, undernutrition, opioids: Suppress GnRH pulses: low LH, FSH and testosterone.
−Continuous GnRH agonist or exogenous androgen: Shuts down LH/FSH: testicular atrophy and low sperm count.

Lab patterns of male hypogonadism

Type	Testosterone	LH / FSH	Classic example
Primary (testicular)	↓	↑ / ↑	Klinefelter syndrome (47,XXY), orchitis, chemotherapy
Tubular damage only	Normal	Normal / ↑	Sertoli-cell damage, after cryptorchidism
Secondary or tertiary	↓	↓ / ↓	Kallmann syndrome, pituitary adenoma, hyperprolactinemia
Exogenous androgen	↑ (exogenous)	↓ / ↓	Anabolic steroid use: small testes, infertility

Clinical notes

Cryptorchidism: a testis left in the warmer abdomen loses germ cells and carries a higher cancer risk; testosterone may stay normal.
Varicocele (usually left, because the left testicular vein drains at a right angle into the renal vein) warms the testis and lowers sperm quality.
Anabolic steroid users present with small testes, low sperm count and gynecomastia (aromatization of the excess androgen).

Test yourself

Think of the answer, then tap the question to see it.

A bodybuilder using testosterone injections has small testes and a very low sperm count. Why, if his testosterone is high?

Exogenous androgen suppresses GnRH, LH and FSH. Leydig cells stop making local testosterone, so the very high intratesticular level that spermatogenesis needs is lost, and the testes shrink.

A man has normal testosterone and LH but raised FSH. Which cell type is failing?

Sertoli cells / the seminiferous tubules: they make inhibin B, the brake on FSH. Leydig cells (LH and testosterone) still work.

Why does continuous GnRH lower testosterone while pulsed GnRH raises it?

Gonadotroph GnRH receptors need pulses; constant exposure down-regulates and desensitizes them, so LH and FSH fall and testosterone falls after an initial flare.

Why is the left side the usual site of a varicocele?

The left testicular vein drains at a right angle into the left renal vein, so pressure is higher; the right drains obliquely into the vena cava.

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See it in 3D

The structures of Durgical's 3D anatomy where it happens.

In Biochemistry

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Educational physiology content; not a diagnostic or treatment guide and no substitute for a health professional's advice. Values are approximate references. No doses are given.

Sources: 27.1 Anatomy and Physiology of the Testicular Reproductive System (OpenStax (Rice University), 2022); 17.8 Gonadal and Placental Hormones (OpenStax (Rice University), 2022); Varicocele (StatPearls (NCBI Bookshelf), 2023); Hall JE. Guyton and Hall Textbook of Medical Physiology, 13th ed. (ch. 81). Reference book used to check facts; its text and figures are not reproduced (Elsevier, 2016).

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Representative model, for educational purposes only.