Hentges S, Boyadjieva N, Sarkar D K
Department of Veterinary and Comparative Anatomy, Washington State University, Pullman 99164-6520, USA.
Endocrinology. 2000 Mar;141(3):859-67. doi: 10.1210/endo.141.3.7382.
Recently, we have shown that transforming growth factor-beta3 (TGFbeta3) mediates estradiol's mitogenic action in primary cultures of mixed anterior pituitary cells. In some cell types, TGFbeta 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 TGFbeta3 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 TGFbeta3 unless RC-4B/C cells were cocultured with FS cells. Enriched lactotropes cocultured with FS cells also demonstrated a proliferative response to TGFbeta3. Media collected from FS cells treated with TGFbeta3 stimulated the proliferation of lactotropes in enriched cultures. TGFbeta3 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 TGFbeta3 action involving cell-to-cell interaction in the anterior pituitary between lactotropes and FS cells during estrogen-induced mitogenesis.
最近,我们已经表明,转化生长因子-β3(TGFβ3)在混合垂体前叶细胞的原代培养中介导雌二醇的促有丝分裂作用。在某些细胞类型中,TGFβ亚型通过增加生长刺激肽生长因子,经由旁分泌机制刺激细胞增殖。本文所呈现的研究对垂体细胞培养中是否存在这样一种机制进行了检测。数据表明,与混合垂体培养中催乳素细胞的反应不同,通过Percoll梯度分离获得的富集催乳素细胞培养物,对TGFβ3处理没有增殖反应。RC-4B/C细胞系的催乳素细胞,该细胞系包含垂体前叶所有分泌激素的细胞类型,但缺乏滤泡星状(FS)细胞,对TGFβ3没有增殖反应,除非RC-4B/C细胞与FS细胞共培养。与FS细胞共培养的富集催乳素细胞也表现出对TGFβ3的增殖反应。用TGFβ3处理FS细胞后收集的培养基刺激了富集培养物中催乳素细胞的增殖。TGFβ3增加了FS细胞碱性成纤维细胞生长因子的释放。FS细胞条件培养基中碱性成纤维细胞生长因子的免疫中和抑制了对催乳素细胞的生长刺激作用。这些数据为TGFβ3作用的一种新机制提供了证据,该机制涉及雌激素诱导的有丝分裂过程中垂体前叶催乳素细胞与FS细胞之间的细胞间相互作用。