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Department of Animal Sciences, Rutgers, State University of New Jersey (N.B., D.K.S.), New Brunswick, New Jersey 08901; and the Departments of Veterinary and Comparative Anatomy (S.H.), 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.
Recently, we have shown that transforming growth factor-ß3 (TGFß3) mediates estradiols mitogenic action in primary cultures of mixed anterior pituitary cells. In some cell types, TGFß 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 TGFß3 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 TGFß3 unless RC-4B/C cells were cocultured with FS cells. Enriched lactotropes cocultured with FS cells also demonstrated a proliferative response to TGFß3. Media collected from FS cells treated with TGFß3 stimulated the proliferation of lactotropes in enriched cultures. TGFß3 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 TGFß3 action involving cell-to-cell interaction in the anterior pituitary between lactotropes and FS cells during estrogen-induced mitogenesis.
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