Opposing Actions of Two Transforming Growth Factor- Isoforms on Pituitary Lactotropic Cell Proliferation

Abstract

Three transforming growth factor-β protein isoforms (TGFβ1, TGFβ2, and TGFβ3) have been identified in mammals. These isoforms appear to have similar actions on cell growth in various tissues. In rat pituitary tissue, TGFβ1 is localized in PRL-secreting lactotropes and has been shown to act on lactotropes to inhibit estradiol-induced cell proliferation. The steroid inhibits the production and secretion of TGFβ1. It is not known whether the other two isoforms are produced in and/or act on lactotropes. Using immunocytochemical detection techniques, we determined that, like TGFβ1, TGFβ3 is colocalized with PRL in the anterior pituitary of Fischer-344 female rats. Administration of estradiol increased TGFβ3-immunoreactive cell numbers, TGFβ3 protein, and TGFβ3 messenger RNA levels in the pituitary. Determinations of TGFβ3 actions in vitro in primary cultures of pituitary cells indicated that TGFβ3 concentration dependently increases lactotropic cell proliferation. The growth-promoting action of TGFβ3 was potentiated by estradiol. Immunoneutralization studies indicated that although TGFβ1 antibody failed to prevent estradiol’s mitogenic action, it potentiated the mitogenic action of TGFβ3. In contrast, TGFβ3-neutralizing antibody inhibited lactotropic cell proliferation by estradiol. These data indicate that unlike many other tissues, TGFβ1 and TGFβ3 have opposite actions on lactotropic proliferation in the pituitary. Furthermore, TGFβ1 and TGFβ3 may be involved in estradiol’s mitogenic action on lactotropes.