Activin and inhibin are closely related protein complexes that have almost directly opposite biological effects.
Inhibins are glycoprotein hormones of which there are two molecular forms, inhibin A and inhibin B.
Known to have a negative feedback effect on pituitary follicle-stimulating hormone secretion.
The fetoplacental unit produces inhibin throughout pregnancy.
Inhibin A is the predominant form of inhibin in maternal circulation from 4 weeks of gestation.
The biological function of inhibin A in pregnancy is unclear.
Inhibin A is a marker of placental function and has a shorter than human chorionic gonadotropin shorter half-life.
Measurement of inhibin A in early pregnancy helps predict miscarriage, Down’s syndrome, preeclampsia, and fetal growth restriction in the first and/or second trimester before the onset of the clinical symptoms.
Inhibin is a protein secreted by granulosa cells in female and Sertoli cells in males in response to FSH, and its major action is the negative feedback control of pituitary FSH secretion.
It is found in blood plasma, and in seminal plasma and follicular fluid.
A dimeric protein of great complexity, with a molecular weight of 32,000 daltons, and consists of one alpha-chain (approx 18 kDa) and one beta-chain (14 kDa) linked by disulphide bridges.
Its subunits alone possess no known biological action.
The inhibin family exists as two separate beta-subunit genes, and thus two distinct proteins: termed the beta-A subunit and the beta-B subunit.
Inhibin-A and. inhibin-B, exist in 7 to 9 different molecular forms.
Not all of the circulating inhibin is in the biologically active form.
Inhibins on the morning of estrus coincides with the peak of FSH, consistent with the negative feedback relationship between FSH and inhibin.
In human follicular fluid, concentrations of inhibin-A change little with follicular diameter development, whereas inhibin-B concentrations rise markedly as follicles develop.
During the menstrual cycle, inhibin-A concentrations are low during the follicular phase, increase after ovulation and increase to a maximum during the mid-luteal phase.
Inhibit A is suggested to be primarily of luteal origin.
In contrast, inhibin-B concentrations are high in the follicular phase, and fall progressively towards ovulation.
This is the inverse of changes in estradiol secretion, but loosely follow the changes observed in FSH secretion.
Females secrete both forms of inhibin.
Males, only appear to synthesize and secrete inhibin-B.
Inhibin secretion is increased by FSH.
In women given single injections of FSH, both inhibin forms are stuimulated, whereas during a FSH-stimulated cycle, plasma concentrations of inhibin-B but not inhibin-A were stimulated; this is consistent with the follicular source of inhibin-B.
Inhibin is a potential mediator of age-related rise in FSH secretion suggesting that inhibin-B concentrations are lower in older women, while inhibin-A and follistatin concentrations change little, and activin concentrations are higher.
Activin and inhibin
Inhibin downregulates FSH synthesis and inhibits FSH secretion.
Inhibin is also a dimer wherein the first component is a beta subunit similar or identical to the beta subunit in activin.
In contrast to activin, the second component of the inhibin dimer is a more distantly-related alpha subunit.
Inhibin inhibits FSH production in both genders, but does not inhibit the secretion of GnRH from the hypothalamus.
Inhibin is produced in the gonads, pituitary gland, placenta, corpus luteum and other organs in females.
FSH stimulates the secretion of inhibin from the granulosa cells of the ovarian follicles.
Subsequently inhibin suppresses FSH.
Inhibin B reaches a peak in the early- to mid-follicular phase.
There is a second peak at ovulation.
Inhibin A reaches its peak in the mid-luteal phase.
Inhibin secretion is diminished by GnRH, and enhanced by insulin-like growth factor-1 (IGF-1).
In males inhibin is secreted from the Sertoli cells, located in the seminiferous tubules inside the testes.
Androgens stimulate inhibin production.
Inhibin may also help to locally regulate spermatogenesis.
An elevated inhibin A, increased beta-hCG, decreased AFP, and a decreased estriol is suggestive of the presence of a fetus with Down syndrome.
Inhibin is also used as a marker for ovarian cancer.
Inhibin B can be used as a marker of spermatogenesis function and male infertility.
Serum inhibin-B weakly indicates presence of sperm cells in the testes.
The mean serum inhibin B level is significantly higher among fertile men than in infertile men.
As men get older, libido declines significantly and is associated with elevated FSH concentrations, although both testosterone and inhibin-B decline with age in similar patterns.
Inhibin-B may be a marker of testicular function.and serum inhibin has been positively correlated with sperm count, testis volume and testis histology.
Inhibin-A is secreted by the feto-placental unit, as evidenced by increased concentrations during pregnancy, with significant increases are observed by 6 – 8 weeks.
Inhibin-A is a potential marker of progression of pregnancy following IVF and embryo transfer.
Multiple pregnancies result in higher inhibin-A concentrations than singleton pregnancies at 8 – 10 weeks.
Evidence exists that inhibin-A secretion is dependent on the presence of a live fetus.
Inhibin-A concentrations do not increase in cases of early fetal loss.
Inhibit-A may thus be a good marker for monitoring IVF pregnancies.
Inhibin-A and inhibin-B concentrations are lower in ovarian follicles from women with polycystic ovarian syndrome (PCOS) compared to healthy follicles.
Plasma inhibin-A and inhibin-B concentrations were reported to be higher in women with PCOS compared to controls.
he pattern of secretion of inhibin is altered in PCOS.
Inhibin-B concentrations are significantly elevated in patients with granulosa cell tumors, but normalize in patients in clinical remission.
Inhibin secretion is not affected by epithelial cell cancers.