Lactotrope differentiation in rats is modulated by a milk-borne signal transferred to the neonatal circulation.

Abstract

We have previously reported that normal differentiation of PRL-secreting cells in neonatal rats requires a maternal signal specific to the first few days of lactation. Subsequently, we found that milk proteins from this period had a greater capacity than those from later in lactation to stimulate lactotrope differentiation in vitro, suggesting that the maternal signal was a milk-borne peptide. We reasoned in the present study that if this were the case, the signal should be present in the serum of suckling pups, and its level should reflect that in mothers' milk. To test this hypothesis, we first compared serum from 3-day-old pups with that from newborn pups that had not yet suckled. Anterior pituitary cells from 1-day-old pups were cultured for 6 days in the presence of various serum samples (0.01-1.0% by volume). Lactotrope differentiation was assessed using a reverse hemolytic plaque assay for PRL. Serum from 3-day-old pups was more effective (P < 0.01; n = 4) than that from unsuckled newborns at stimulating lactotrope differentiation in vitro (to 3.5 +/- 0.5% and 1.5 +/- 0.5% of all anterior pituitary cells, respectively). Next, we tested whether this increase in serum bioactivity in 3-day-old pups required maternal influences restricted to the first few days of lactation. Newborn pups were placed with foster mothers that had been lactating for 0 or 7 days. When the pups were 3 days old, their serum was tested for lactotrope-differentiating activity. Serum from pups placed with day 0 foster mothers (control) increased the abundance of PRL cells to 2.4 +/- 0.3% of all cells (P < 0.01; n = 3), whereas serum from pups placed with day 7 foster mothers failed to stimulate lactotrope differentiation. In similar experiments, litters placed the day after birth with day 7 foster mothers were separated on day 3 postpartum for 3 h, after which littermates were allowed to suckle for 90 min on different foster mothers on day 3 or 9 of lactation. This brief suckling bout increased (P < 0.01; n = 3) the capacity of serum from pups on day 3 mothers to stimulate PRL cell differentiation (to 3.9 +/- 0.4%) above that of serum from littermates placed with day 9 foster mothers (to 1.8 +/- 0.2%). Finally, the differentiating activities in pup serum and mothers' milk eluted from gel filtration chromatography in identical fractions (4-8 kilodaltons).(ABSTRACT TRUNCATED AT 400 WORDS)