STIMULATION OF LACTOTROPE DIFFERENTIATION IN-VITRO BY FIBROBLAST GROWTH-FACTOR

We have reported previously that differentiation of PRL-secreting cells in rats is regulated by a maternal peptide transferred to the neonatal circulation after ingestion of mothers' milk. Inasmuch as milk contains numerous hormones and biologically active peptides, the present study was designed to test the capacity of various growth factors and hypothalamic peptides at inducing the differentiation of PRL cells in vitro. Anterior pituitary cells from 1-day-old rat pups were cultured in a serum-free system for 6 days with a wide concentration range of each test peptide. After this culture period, lactotrope differentiation was assessed by subjecting the anterior pituitary cells to reverse hemolytic plaque assays for PRL. Our efforts were focused on those growth factors and hypophysiotropic peptides found in milk and/ or known to regulate pituitary function. Included among these were TRH, GH-releasing factor, somatostatin, vasoactive intestinal peptide, angiotensin-II, insulin-like growth factor-I and -II, LH-releasing hormone, arginine vasopressin, and acidic and basic fibroblast growth factors (aFGF and bFGF, respectively). Of these peptides, only aFGF and bFGF were capable of stimulating lactotrope differentiation. Specifically, we found that maximally effective concentrations of aFGF and bFGF increased the percentage of PRL-releasing cells by almost 8-fold, from about 0.5% to over 4% of all pituitary cells. In addition, bFGF was found to be about 10-fold more potent than aFGF at inducing the differentiation of PRL secretors, with minimum effective doses approaching 10-(11) and 10(-10) M for bFGF and aFGF, respectively. These results suggest that bFGF is a strong candidate to subserve a role in regulating the differentiation of lactotropes in vivo.