Stimulation of prolactin cell differentiation in vitro by a milk-borne peptide.

We have previously reported that the normal expression of PRL-secreting cells in neonatal rats requires a maternal signal specific to the first few days of lactation. These results raised the possibility that a milk-borne factor(s) ingested by the neonate and absorbed into the circulation might induce the ontogenic appearance of PRL cells. The purpose of the present study was to determine whether milk from this period could directly stimulate the differentiation of PRL secretors in culture. Monodispersed anterior pituitary cells from 1-day-old pups were cultured for 6 days with aqueous extracts of milk from early (days 2, 3, and 4) and late (days 15 and 16) lactation and then subjected to reverse hemolytic plaque assays for PRL and GH release. We found that the addition of milk extracts (10 mg/ml) from either early or late lactation stimulated the differentiation of PRL secretors (to 6.1 +/- 1.0% and 2.4 +/- 0.7% of all pituitary cells, respectively; mean +/- SE; n = 3) above that in control cultures without milk (0.2 +/- 0.2%). Thus, early milk was more than twice as effective as late milk in this regard (P less than 0.05). This effect appeared to be specific to PRL cell differentiation, since the relative abundance of GH secretors was not different between cells treated with either early or late milk (29.3 +/- 4.8% and 33.7 +/- 3.9%, respectively). On the other hand, late milk was more than twice as effective as early milk at increasing the capacity of GH secretors to release hormone (P less than 0.05). Preliminary characterization by gel filtration chromatography and proteolytic hydrolysis indicates that the bioactivity that differentiates PRL secretors is a small peptide(s) of 2000-6000 daltons. Taken together, our results demonstrate that a milk-borne peptide(s) is capable of specifically stimulating the differentiation of PRL-secreting cells in vitro, and that this bioactivity is more prevalent in milk from early lactation.