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

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Abstract
Three transforming growth factor-b protein isoforms (TGFb1, TGFb2, and TGFb3) have been identified in mammals. These iso- forms appear to have similar actions on cell growth in various tissues. In rat pituitary tissue, TGFb1 is localized in PRL-secreting lacto- tropes and has been shown to act on lactotropes to inhibit estradiol- induced cell proliferation. The steroid inhibits the production and secretion of TGFb1. 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 TGFb1, TGFb 3i s colocalized with PRL in the anterior pituitary of Fischer-344 female rats. Administration of estradiol increased TGFb3-immunoreactive cell numbers, TGFb3 protein, and TGFb3 messenger RNA levels in the pituitary. Determinations of TGFb3 actions in vitro in primary cultures of pituitary cells indicated that TGFb3 concentration de- pendently increases lactotropic cell proliferation. The growth- promoting action of TGFb3 was potentiated by estradiol. Immuno- neutralization studies indicated that although TGFb1 antibody failed to prevent estradiol's mitogenic action, it potentiated the mitogenic action of TGFb3. In contrast, TGFb3-neutralizing antibody inhibited lactotropic cell proliferation by estradiol. These data indicate that unlike many other tissues, TGFb1 and TGFb3 have opposite actions on lactotropic proliferation in the pituitary. Furthermore, TGFb1 and TGFb3 may be involved in estradiol's mitogenic action on lactotropes. (Endocrinology 141: 1528 -1535, 2000)

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