FOLLISTATIN DECREASES ACTIVIN-STIMULATED FSH-SECRETION WITH NO EFFECTON GNRH-STIMULATED FSH-SECRETION IN PREPUBERTAL MALE MONKEYS

Follistatin is an activin-binding glycoprotein that decreases FSH secr etion in vitro and in vivo in rats. The mechanism by which follistatin acts is unclear, but it has been suggested that it may bind endogenou s activin and neutralize its effects. In this study, we wished to test the ability of follistatin to suppress FSH secretion in vivo in prima tes whose FSH secretion has been stimulated by activin or by GnRH. Six prepubertal male monkeys were injected intravenously with human recom binant tollistatin at the dose of 90 mug/kg or 180 mug/kg plus activin (90 mug/kg) or GnRH (10 mug/kg). Frequent blood samples were drawn fo r 12 hours following each injection. Bio FSH and LH levels were measur ed in those samples. GnRH and activin each stimulated FSH bioactivity. Both doses of follistatin significantly inhibited the activin-induced increase in FSH (p<0.05). The GnRH-induced increase in FSH was not af fected by follistatin. LH levels were not affected by follistatin in a ny of the studies. These data suggest that follistatin can suppress th e activin-induced increase in FSH in primates and is consistent with t he hypothesis that follistatin can block the physiological effects of endogenous activin in primates. This effect is likely to be due to the binding of follistatin to activin either in the peripheral circulatio n or at the pituitary level.