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Opposing Actions of Two Transforming Growth Factor-ß Isoforms on Pituitary Lactotropic Cell Proliferation¹

Department of Animal Sciences, Rutgers, State University of New Jersey (A.D., N.B., D.K.S.), New Brunswick, New Jersey 08901; and Departments of Veterinary and Comparative Anatomy (S.H., M.P.), and Pharmacology and Physiology, Washington State University, Pullman, Washington 99164-6520

Address all correspondence and requests for reprints to: Dr. D. K. Sarkar, Department of Animal Sciences, Rutgers, State University of New Jersey, New Brunswick, New Jersey 08901.

Three transforming growth factor-ß protein isoforms (TGFß1, TGFß2, and TGFß3) have been identified in mammals. These isoforms appear to have similar actions on cell growth in various tissues. In rat pituitary tissue, TGFß1 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 TGFß1. 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 TGFß1, TGFß3 is colocalized with PRL in the anterior pituitary of Fischer-344 female rats. Administration of estradiol increased TGFß3-immunoreactive cell numbers, TGFß3 protein, and TGFß3 messenger RNA levels in the pituitary. Determinations of TGFß3 actions in vitro in primary cultures of pituitary cells indicated that TGFß3 concentration dependently increases lactotropic cell proliferation. The growth-promoting action of TGFß3 was potentiated by estradiol. Immunoneutralization studies indicated that although TGFß1 antibody failed to prevent estradiol’s mitogenic action, it potentiated the mitogenic action of TGFß3. In contrast, TGFß3-neutralizing antibody inhibited lactotropic cell proliferation by estradiol. These data indicate that unlike many other tissues, TGFß1 and TGFß3 have opposite actions on lactotropic proliferation in the pituitary. Furthermore, TGFß1 and TGFß3 may be involved in estradiol’s mitogenic action on lactotropes.

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