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-es tradiol (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 pro perties of the anterior pituitary lactotroph. At a low population dens ity (10500 cells/cm(2)), E(2) stimulated production of IGF-I by 4.2-fo ld. At this density, the antiestrogen tamoxifen (TAM) had no significa nt 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 stimul ated GH(4)C(1) cell proliferation at this population density. At a fou r-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 prol iferation of GH(4)C(1) cells at high density, and T-3 stimulated proli feration to a lesser extent than observed at the low density. At the l ow population density, E(2) and T-3 stimulated production of IGFBP-3 b y 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 da ta 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 populatio n density.