Opposing actions of two transforming growth factor-beta isoforms on pituitary lactotropic cell proliferation

Three transforming growth factor-beta protein isoforms (TGF beta 1, TGF bet a 2, and TGF beta 3) have been identified in mammals. These isoforms appear to have similar actions on cell growth in various tissues. In rat pituitar y tissue, TGF beta 1 is localized-in PRL-secreting lactotropes and has been shown to act on lactotropes to inhibit estradiol-induced cell proliferatio n. The steroid inhibits the production and secretion of TGF beta 1. It is n ot known whether the other two isoforms are produced in and/or act on lacto tropes. Using immunocytochemical detection techniques, we determined that, hire TGF beta 1, TGF beta 3 is colocalized with PRL in the anterior pituita ry of Fischer-344 female rats. Administration of estradiol increased TGF be ta 3-immunoreactive cell numbers, TGF beta 3 protein, and TGF beta 3 messen ger RNA levels in the pituitary. Determinations of TGF beta 3 actions in vi tro in primary cultures of pituitary cells indicated that TGF beta 3 concen tration dependently increases lactotropic cell proliferation The growth-pro moting action of TGF beta 3 was potentiated by estradiol. Immunoneutralizat ion studies indicated that although TGF beta 1 antibody failed to prevent e stradiol's mitogenic action, it potentiated the mitogenic action of TGF bet a 3. In contrast, TGF beta 3-neutralizing antibody inhibited lactotropic ce ll proliferation by estradiol. These data indicate that unlike many other t issues, TGF beta 1 and TGF beta 3 have opposite actions on lactotropic prol iferation in the pituitary. Furthermore, TGF beta 1 and TGF beta 3 may be i nvolved in estradiol's mitogenic action on lactotropes.