Induction of classical lactotropes by epidermal growth factor in rat pituitary cell cultures

Long term incubation of pituitary tumor GH3 cultures with epidermal growth factor (EGF) induces reciprocal changes in PRL and GH production. However, it is not known whether EGF alters the cellular composition of these cultures. Another unanswered question is whether chronic treatment with EGF stimulates PRL secretion from nonneoplastic pituitary cells. In this study, GH3 cells and pituitary cells from neonatal (10-day-old) rats were cultured for 6 and 2 days, respectively, in the absence or presence of 5 nM EGF. Cells containing PRL and/or GH were then enumerated using light microscopic immunocytochemistry. In addition, neonatal pituitary cells were subjected to reverse hemolytic plaque assays for PRL. EGF treatment drastically increased the proportion of classical lactotropes (cells that secrete only PRL) in the GH3 cultures, from about 0.5% to 8% of all cells, without modifying the percentage of GH-positive cells. A similar action of EGF was observed in the primary cultures. Moreover, EGF enhanced by 240% the amount of PRL secreted from the neonatal lactotrope population during 1-h incubations under basal conditions. This effect was mediated by a selective increase in the relative number of PRL secretors forming large plaques. The results suggest that EGF promotes the differentiation of classical lactotropes in both GH3 cultures and pituitary cultures from neonatal rats, and that these cells are characterized by a high basal rate of PRL secretion.