ESTRADIOL AND TRIIODOTHYRONINE INCREASE PRODUCTION OF INSULIN-LIKE GROWTH-FACTOR-I (IGF-I) AND INSULIN-LIKE GROWTH-FACTOR BINDING PROTEIN-3 (IGFBP-3) BY GH(4)C(1) RAT PITUITARY-TUMOR CELLS

The main purpose of this study was to examine the effect of 17 beta-estradiol (E(2)) on the production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) by GH(4)C(1) cells, a pituitary tumor cell line that displays many phenotypic properties of the anterior pituitary lactotroph. At a low population density (10500 cells/cm(2)), E(2) stimulated production of IGF-I by 4.2-fold. At this density, the antiestrogen tamoxifen (TAM) had no significant effect, whereas triiodothyronine (T-3), which has been demonstrated to increase the level of IGF-I mRNA in the parental GH(3) cell line, stimulated IGF-I production by 3.3-fold. Both E(2) and T-3 also stimulated GH(4)C(1) cell proliferation at this population density. At a four-fold higher population density (42 000 cells/cm(2)), E(2) TAM and T-3 had little effect on IGF-I production. E(2) failed to stimulate proliferation of GH(4)C(1) cells at high density, and T-3 stimulated proliferation to a lesser extent than observed at the low density. At the low population density, E(2) and T-3 stimulated production of IGFBP-3 by 6- and 11-fold, respectively. At high density, the abilities of E(2) and T-3 to stimulate IGFBP3 production were somewhat reduced. TAM had no effect on IGFBP3 production at either population density. These data indicate that E(2) and T-3 Stimulate production by GH(4)C(1) cells of IGF-I through a mechanism that is sensitive to changes in population density.