Inhibin B

A peptide hormone secreted by Sertoli cells of the testis that closes the FSH–Sertoli feedback loop. The clearest single marker of how the seminiferous tubule wall is doing, and one of the most useful labs in male reproductive medicine despite being routinely underordered.

What it is

Inhibin B is a heterodimer — an α-subunit linked by a disulfide bond to a βB-subunit. It belongs to the TGF-β superfamily of growth and differentiation factors. The α-subunit is shared with inhibin A (which has a βA-subunit instead); the βB-subunit is shared with the activins — physically related molecules that drive opposing physiological actions on FSH (inhibins suppress, activins stimulate). The family is structurally tangled in a way that turns out to matter mechanistically.

The “B” distinguishes it from inhibin A, which dominates in females. In males, inhibin B is essentially the entire inhibin signal; in females, both forms appear at different cycle phases.

Source

Almost entirely Sertoli cells, with minor contributions from germ cells and Leydig cells. Production requires FSH stimulation — Sertoli cells in an FSH-deficient state make very little inhibin B, which is why central hypogonadism produces low inhibin B even though the Sertoli compartment itself may be intact.

What it does

Inhibin B closes the feedback loop between the Sertoli compartment and the pituitary gonadotropes. The mechanism is indirect but elegant:

1. FSH from the pituitary stimulates Sertoli cells to make inhibin B.
2. Inhibin B circulates to the pituitary.
3. At the gonadotrope, inhibin B does not directly repress the FSH gene. Instead, it blocks the action of activin — an autocrine factor produced locally by pituitary cells that normally drives FSH-β subunit transcription.
4. With activin blocked, FSH production falls.

The result is the same (FSH down) but the architecture is a competing-ligands model rather than a simple repressor. This is part of why inhibin B’s effect on FSH is graded rather than all-or-nothing — the more inhibin B, the more activin gets competed away.

Critically, inhibin B affects FSH specifically, not LH. LH has its own feedback loop (testosterone through the hypothalamus). This sex-steroid-vs-peptide split is part of why FSH and LH can dissociate on labs — they answer to different feedback signals; see LH-preferential dissociation for the clinical consequences.

Across the lifespan

The trajectory tracks Sertoli activity and FSH drive across the developmental arc:

• Fetal: detectable from second trimester onward as Sertoli cells differentiate.
• Minipuberty: high — peaks at around 3–6 months as Sertoli cells proliferate under postnatal FSH stimulation.
• Childhood: declines to a low-but-detectable baseline. Sertoli cells are quiet but present.
• Gonadarche / early puberty: rises as FSH stimulates Sertoli proliferation and the cells respond.
• Mid-puberty onward: reaches and holds the adult range.
• Aging: declines gradually, paralleling slow Sertoli decline.

Clinical uses

Because inhibin B is a stable measurement — unlike pulsatile LH with its 20–30 minute half-life — and reflects Sertoli function directly, a single morning draw is meaningful and a trend across visits is even more so.

• Tracking pubertal progression — the inhibin B trend across visits is often more interpretable than gonadotropins alone (see the gonadarche tracking panel).
• CDGP vs CHH discrimination — preserved inhibin B argues against severe CHH; very low inhibin B raises the concern. The single best lab marker for this question.
• Anorchia vs cryptorchidism in young children — undetectable inhibin B (paired with undetectable AMH) is strong evidence that no testes exist anywhere.
• Male infertility workup — correlates with spermatogenesis better than FSH does. Preserved inhibin B with elevated FSH suggests an isolated germ-cell problem with intact Sertoli function.
• Klinefelter syndrome — falls in adolescence as Sertoli cells fail; one of the early screening signals before testosterone drops.
• Sertoli cell tumors — many produce inhibin B; an elevated level with a testicular mass is suggestive.
• Cancer-therapy follow-up — falls when chemotherapy or radiation damages the seminiferous epithelium; tracked in fertility-preservation conversations.

Discovery

The existence of an “FSH-inhibiting factor from the testis” was hypothesized by McCullagh in 1932 when he noticed that lipid extracts of bovine testis suppressed pituitary function. The actual protein was not isolated until 1985, independently and almost simultaneously by groups led by Mason at Genentech and Robertson in Melbourne. The B form was characterized in the late 1980s, and clinical assays became widely available in the late 1990s.

Key idea

Inhibin B is the gonad-side voice in the FSH–Sertoli conversation. Where FSH says “how hard is the pituitary pushing the Sertoli compartment,” inhibin B says “how is the Sertoli compartment responding.” A single value is informative; a trend across visits is often the clearest signal in an otherwise ambiguous pubertal or fertility workup.