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 17 beta-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 proliferation to a lesser extent than observed at the low density. At the low population density, E2 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.
Gilchrist
C A
CA
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha 68198-6805, USA.
Park
J H
JH
MacDonald
R G
RG
Shull
J D
JD
D000818:Animals; D002452:Cell Count; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D004965:Estrogen Antagonists / Q000494:pharmacology; D018972:Insulin-Like Growth Factor Binding Protein 3 / Q000096:biosynthesis*; D007334:Insulin-Like Growth Factor I / Q000032:analysis / Q000096:biosynthesis*; D010903:Pituitary Gland, Anterior / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D013629:Tamoxifen / Q000494:pharmacology; D014284:Triiodothyronine / Q000494:pharmacology*
D004965:Estrogen Antagonists; D018972:Insulin-Like Growth Factor Binding Protein 3; D014284:Triiodothyronine; D013629:Tamoxifen; D004958:Estradiol; D007334:Insulin-Like Growth Factor I