Within the first few days of neonatal life in the rat, a milk-borne pe
ptide is transferred to the neonatal circulation and transported to th
e pituitary gland where it acts directly to induce final differentiati
on of mammotropes. As we were attempting to purify this stimulatory pe
ptide, we separated an antagonistic activity that serves as the focus
of the present study. Milk obtained on days 2-3 of lactation was subje
cted to pH fractionation followed by acetone precipitation to yield tw
o fractions that stimulated and inhibited, respectively, mammotrope di
fferentiation in cultures of neonatal pituitary cells. The stimulatory
agent more than doubled the proportion of prolactin secretors in thos
e cultures, whereas the inhibitory agent exerted the opposite effect w
hen tested alone. Moreover, the inhibitory agent severely attenuated m
ammotrope differentiation evoked by the stimulatory fraction or by bas
ic FGF, an established inducer of this developmental phenomenon, The d
iscovery of a milk-borne inhibitor, coupled with the previously descri
bed milk stimulatory factor, indicates that maternal control of mammot
rope differentiation is considerably more sophisticated than previousl
y believed.