A milk-borne factor inhibits mammotrope differentiation in the neonatal rat

Within the first few days of neonatal life in the rat, a milk-borne peptide is transferred to the neonatal circulation and transported to the pituitary gland where it acts directly to induce final differentiation of mammotropes. As we were attempting to purify this stimulatory peptide, we separated an antagonistic activity that serves as the focus of the present study. Milk obtained on days 2-3 of lactation was subjected to pH fractionation followed by acetone precipitation to yield two fractions that stimulated and inhibited, respectively, mammotrope differentiation in cultures of neonatal pituitary cells. The stimulatory agent more than doubled the proportion of prolactin secretors in those cultures, whereas the inhibitory agent exerted the opposite effect when tested alone. Moreover, the inhibitory agent severely attenuated mammotrope differentiation evoked by the stimulatory fraction or by basic FGF, an established inducer of this developmental phenomenon. The discovery of a milk-borne inhibitor, coupled with the previously described milk stimulatory factor, indicates that maternal control of mammotrope differentiation is considerably more sophisticated than previously believed.