Estradiol and triiodothyronine increase production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding protein-3 (IGFBP-3) by GH₄C₁ rat pituitary tumor cells

The main purpose of this study was to examine the effect of 17β-estradiol (E₂) on the production of insulin-like growth factor-I (IGF-I) and insulin-like growth factor binding proteins (IGFBP) by GH₄C₁ cells, a pituitary tumor cell line that displays many phenotypic properties of the anterior pituitary lactotroph. At a low population density (10 500 cells/cm²), E₂ stimulated production of IGF-I by 4.2-fold. At this density, the antiestrogen tamoxifen (TAM) had no significant effect, whereas triiodothyronine (T₃), which has been demonstrated to increase the level of IGF-I mRNA in the parental GH₃ cell line, stimulated IGF-I production by 3.3-fold. Both E₂ and T₃ also stimulated GH₄C₁ cell proliferation at this population density. At a four-fold higher population density (42 000 cells/cm²), E₂, TAM and T₃ had little effect on IGF-I production. E₂ failed to stimulate proliferation of GH₄C₁ cells at high density, and T₃ stimulated production of IGFBP-3 by 6- and 11-fold, respectively. At high density, the abilities of E₂ and T₃ to stimulate IGFBP-3 production were somewhat reduced. TAM had no effect on IGFBP-3 production at either population density. These data indicate that E₂ and T₃ stimulate production by GH₄C₁ cells of IGF-I through a mechanism that is sensitive to changes in population density.