Inhibin A: Mechanism, Dosing & Research Data

Inhibin A is a dimeric glycoprotein (alpha/beta-A subunit) of the TGF-beta superfamily produced predominantly by ovarian granulosa cells in females and Sertoli cells in males. It is the major FSH-suppressing hormone of the luteal phase and early pregnancy, and its measurement in maternal serum (together with AFP, hCG, and estriol) forms the "quad screen" for Down syndrome prenatal diagnosis.

Mechanism of Action

Binds betaglycan on pituitary gonadotrophs, which presents inhibin to ACVR2A/2B; this complex suppresses activin-stimulated FSH beta-subunit gene transcription
Inhibin A and activin A are mutual functional antagonists: inhibin A promotes FSH suppression while activin A promotes FSH release; ovarian corpus luteum shifts balance toward inhibin A after ovulation
Luteal phase dominant inhibin: corpus luteum secretes high inhibin A, suppressing FSH during the second half of the cycle and preventing new follicle recruitment
Early pregnancy: placental inhibin A rises 10-fold in first trimester, suppressing pituitary FSH to prevent additional ovulation
Elevated inhibin A in Down syndrome placentas: the molecular basis of the quad screen positive finding

Research Findings

Down syndrome screening: maternal serum inhibin A elevated ~2-fold (2 MoM) in Down syndrome pregnancies; addition to triple screen increased sensitivity from 69% to 81% at 5% false positive rate
Menopause marker: inhibin A declines to undetectable levels 3-5 years before last menstrual period; precedes FSH rise and AMH decline as the earliest measurable change
Inhibin A elevation in granulosa cell tumors of the ovary: serum inhibin A is the most specific tumor marker for these tumors (>90% sensitivity) and used for monitoring recurrence
Male fertility: Sertoli cell-derived inhibin B (not inhibin A) is the dominant FSH suppressor in males; inhibin A is predominantly female
Recombinant inhibin A reversal of FSH: exogenous inhibin A infusion in GnRH-antagonist treated women suppressed residual FSH, demonstrating direct pituitary action

Research Protocols

Quad screen (prenatal diagnosis): serum inhibin A measurement at 15-20 weeks gestation; integrate with AFP, hCG, estriol for Down syndrome risk calculation
Granulosa cell tumor surveillance: serum inhibin A at diagnosis and every 3-6 months post-treatment; rising levels indicate recurrence
Ovarian reserve research: inhibin A + inhibin B together with FSH and AMH in reproductive aging cohort studies
In vitro receptor assay: recombinant inhibin A at 1-100 ng/mL on pituitary gonadotroph cultures; measure FSH suppression by RIA or ELISA

Interactions

Activin A: functional antagonist; inhibin A sequesters ACVR2A/2B away from activin, preventing activin-driven FSH stimulation
FSH: suppressed by inhibin A; inhibin A elevation is the primary mechanism for FSH suppression in the luteal phase
AMH: complementary ovarian reserve marker; AMH reflects follicle pool quantity, inhibin A reflects corpus luteum function

Safety Profile

Endogenous glycoprotein; not therapeutically administered. Serum measurement is a safe routine diagnostic test. Elevated in granulosa cell tumors; monitoring application. Decreased in menopause and premature ovarian failure. Not for exogenous administration.