AMH — Anti-Müllerian Hormone

A peptide hormone made by Sertoli cells in males and ovarian granulosa cells in females. The hormone that wires the male reproductive anatomy in utero — by causing the Müllerian duct system to regress — and afterwards a marker of Sertoli reserve through childhood and of ovarian reserve through adulthood.

Also called Müllerian Inhibiting Substance (MIS) or Müllerian Inhibiting Hormone (MIH) in the older literature.

What it is

A homodimer — two identical AMH protein chains joined by disulfide bonds. Like inhibin B, it belongs to the TGF-β superfamily of growth and differentiation signaling proteins, but it acts through its own dedicated receptor (AMH-receptor type II) rather than through the inhibin/activin receptors.

Source

• Males: Sertoli cells, from week 8 of gestation onward.
• Females: granulosa cells of small growing follicles (preantral and early antral), from late fetal life onward.

The fetal role

The classical role, and the reason for the name. In the male fetus:

1. Sertoli cells begin producing AMH starting around week 8 of gestation.
2. AMH binds the AMH-type-II receptor on cells of the Müllerian duct.
3. The Müllerian ducts undergo apoptosis and regress.
4. Without this signal — as in 46,XX embryos, which have no Sertoli cells — the Müllerian ducts persist and become the fallopian tubes, uterus, and upper vagina.

This is the “no-Müllerian” half of the male program. The other halves are testosterone (which preserves the Wolffian ducts as epididymis, vas deferens, seminal vesicles) and DHT (which builds the external genitalia). See fetal sex differentiation for the full cascade.

Failure of AMH signaling produces Persistent Müllerian Duct Syndrome (PMDS) — 46,XY individuals with otherwise normal male anatomy who also have internal Müllerian structures (a small uterus, fallopian tubes). Often discovered incidentally during inguinal hernia surgery in childhood, since the Müllerian remnants may herniate. Caused by mutations in the AMH gene or its receptor.

The postnatal role

After the Müllerian system has regressed (in males) or developed (in females), AMH continues to be produced — but its function shifts.

In males

A marker of Sertoli cell number and immaturity. High when Sertoli cells are immature and proliferating; falls as they mature. The rising intratesticular testosterone of puberty is what drives the fall — mature Sertoli cells under high androgen exposure switch off AMH production.

This produces an inverse pattern to inhibin B: as the Sertoli compartment matures during puberty, AMH falls and inhibin B rises. The two together give the Sertoli differentiation state:

Stage	AMH	Inhibin B	Sertoli state
Fetal	high	detectable	immature, dividing
Minipuberty	very high	high	proliferating
Childhood	high	low-moderate	immature, quiescent
Early puberty	begins to fall	rising	starting to mature
Mid-late puberty	falling	high	maturing, supporting spermatogenesis
Adult	low	adult range, stable	mature, fully differentiated
Late life	very low	gradually falling	aging

The crossover during puberty — AMH falling, inhibin B rising — is one of the clearest endocrine signatures of Sertoli cell maturation.

In females

A marker of the pool of small growing follicles — the ovarian reserve. AMH is made by granulosa cells of follicles that have started to grow but have not yet been recruited for ovulation. The total AMH level integrates across the whole growing pool, so it reflects how many follicles remain available. AMH declines gradually across the reproductive years and reaches near-zero at menopause.

Across the lifespan (males)

The opposite trajectory of inhibin B:

• Fetal: rises rapidly from week 8 to drive Müllerian regression.
• Minipuberty: very high.
• Childhood: stays high — the lab signature of an intact prepubertal testis.
• Puberty: falls dramatically as Sertoli cells mature under rising intratesticular testosterone.
• Adult: low.
• Late life: very low.

Clinical uses

In males

• Disorders of sex development workup — including PMDS, ambiguous genitalia, and 46,XY karyotypes with discordant phenotype.
• Anorchia vs cryptorchidism in infants and young children — undetectable AMH (paired with undetectable inhibin B) is strong evidence that no testes exist. AMH is particularly useful here because it is high in normal childhood, so undetectable is starkly abnormal — whereas childhood inhibin B is already low.
• Tracking Sertoli function in prepubertal years when other markers are flat.
• Klinefelter syndrome — falls more steeply than expected in adolescence.
• Sertoli cell tumors — many produce AMH.
• Cancer-therapy follow-up — tracking gonadal damage in boys treated with chemotherapy or radiation.

In females

• Ovarian reserve assessment — predicts response to IVF stimulation.
• PCOS workup — often elevated, reflecting many small follicles that fail to mature.
• Menopause prediction — declines for years before cycles cease.
• Fertility-preservation counseling — gives a relative sense of remaining reproductive window.

Discovery

The Müllerian-inhibiting effect was inferred by Alfred Jost in 1947 from classic castration experiments in fetal rabbits. He showed that removing fetal testes led to Müllerian persistence even when external androgens were provided — demonstrating that a separate signal from the testis (beyond testosterone) was responsible for Müllerian regression. The actual AMH protein was cloned by Cate and colleagues in 1986. Postnatal clinical uses (fertility, DSD workup) emerged in the 1990s and 2000s.

Key idea

AMH defines maleness in utero — by deleting the alternative anatomy rather than by building male anatomy itself. After that decisive fetal role, it spends the rest of life as a marker of cellular state: in males, the maturity of the Sertoli compartment; in females, the size of the follicular reserve. The trajectory across male puberty (high → low, inversely tracking inhibin B) is one of the clearest endocrine signatures of Sertoli cell differentiation.