Transforming growth factor-β3 stimulates lactotrope cell growth by increasing basic fibroblast growth factor from folliculo-stellate cells

Recently, we have shown that transforming growth factor-beta 3 (TGF beta 3) mediates estradiol's mitogenic action in primary cultures of mixed anterior pituitary cells. In some cell types, TGF beta isoforms stimulate cell proliferation via a paracrine mechanism by increasing growth stimulatory peptide growth factors. Whether such a mechanism exists in pituitary cell culture was examined in the studies presented here. The data demonstrate that unlike the response of lactotropes in mixed pituitary cultures, cultures of enriched lactotropes, obtained by Percoll gradient separation, did not proliferate in response to TGF beta 3 treatment. The lactotropic cells of the RC-4B/C cell line, a cell line that contains all of the hormone-secreting cell types of the anterior pituitary but is devoid of folliculo-stellate (FS) cells, did not proliferate in response to TGF beta 3 unless RC-4B/C cells were cocultured with FS cells. Enriched lactotropes cocultured with FS cells also demonstrated a proliferative response to TGF beta 3. Media collected from FS cells treated with TGF beta 3 stimulated the proliferation of lactotropes in enriched cultures. TGF beta 3 increased the release of basic fibroblast growth factor from FS cells. Immunoneutralization of basic fibroblast growth factor in FS cell-conditioned medium inhibited the growth stimulatory action on lactotropes. These data provide evidence for a novel mechanism of TGF beta 3 action involving cell-to-cell interaction in the anterior pituitary between lactotropes and FS cells during estrogen-induced mitogenesis.