Growth factors secreted by the GH3 rat pituitary tumor cell line. Study of their autocrine mitogenic activity in cultured GH3 cells, A431 cells and human fibroblasts.

The pathogenesis of pituitary tumors is still controversial. Little is known about the effects of growth factors on pituitary growth, despite most of them having well-documented mitogenic actions in other tissues. We have investigated the secretion of growth factors by the rat pituitary tumor cell line, GH3 and also have studied their mitogenic effects in other two non-pituitary human cell lines, A431 and fibroblasts. Size-exclusion chromatography of acidic extracts of GH3 cells yielded two peaks of mitogenic activity when GH3 cells were used as potential targets. One peak of growth-promoting activity (> 5 KDa) stimulated [3H] thymidine incorporation into GH3 cells (201% above control). Another peak (2-3 KDa) also stimulated [3H] thymidine incorporation into GH3 cells (162% above control). The first peak of autocrine action represented 60% and the second one, 40% of the total peaks mitogenic activity. GH3 pooled fractions A, B, C, D, corresponding to the GH3 peaks of autocrine growth-stimulating activity significantly enhanced [3H] thymidine incorporation into A431 cells and human fibroblasts. In A431 cells, the first peak of mitogenic activity represented 46.7%, and the second one, 53.2% from the total peaks mitogenic activity. In fibroblasts, the GH3 pooled fractions produced just one peak of growth-stimulating activity, which increased [3H] thymidine incorporation (175% above control). Our data provide the indications that (1) cultured rat pituitary tumor cells GH3 secrete two autocrine growth factors which may have a role on their development and maintenance; (2) these factors, which have yet to be characterized, are potent mitogens for malignant non-pituitary cells such as human squamous carcinoma cell line, A431, as well as for human fibroblast cell line.