title: The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen.
abstract: The GH3 pituitary cell line has been used to investigate the role of the oestrogen receptor (ER) as a modulator of mitogenic signals in tumour cells in the absence of exogenous oestrogen. Using a chemically defined, serum- and oestrogen-free medium, we have demonstrated that the pure steroidal anti-oestrogens ICI 182780 and ICI 164384 are capable of blocking growth by more than 50% after 5 days of culture. Studies with conditioned medium have indicated that the basal growth is due to the secretion of autocrine growth stimulatory substances. Under serum- and oestrogen-free conditions, insulin and IGF-I increased the growth rate of these cells by twofold over a 5-day treatment period, and this effect was also blocked by the anti-oestrogens ICI 182780 and ICI 164384 (50% of maximum inhibition at 0.6 and 6 nM respectively). To explore the potential mechanism by which the ER apparently facilitates the growth factor effects under oestrogen-free conditions, GH3 cells were transiently transfected with a plasmid reporter containing the vitellogenin oestrogen response element (delta MTV-ERE-LUC). We have shown that as well as oestradiol (OE2), insulin and IGF-I induce luciferase activity by between two- and sevenfold (four experiments), and these effects were completely blocked by ICI 182780. In contrast, growth factors and OE2 were unable to induce luciferase expression when transfections were performed with a plasmid reporter lacking the oestrogen response element. The studies presented here strongly suggest that, in the absence of oestrogen, the ER in these pituitary tumour cells has a role in growth, as peptide factors are able to induce its conversion to a state which is capable of up-regulating the transcription of key growth-promoting genes.
authors.affiliation: Max-Planck Institute of Psychiatry, Clinical Institute, Munich, Germany.
authors.forename: C J
authors.initials: CJ
authors.lastname: Newton
authors.forename: T
authors.initials: T
authors.lastname: Trapp
authors.forename: U
authors.initials: U
authors.lastname: Pagotto
authors.forename: U
authors.initials: U
authors.lastname: Renner
authors.forename: R
authors.initials: R
authors.lastname: Buric
authors.forename: G K
authors.initials: GK
authors.lastname: Stalla
mesh_terms: D000818:Animals; D001483:Base Sequence; D002455:Cell Division / Q000187:drug effects; D016895:Culture Media, Serum-Free; D004958:Estradiol / Q000031:analogs & derivatives / Q000494:pharmacology; D000077267:Fulvestrant; D007328:Insulin / Q000494:pharmacology; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors / Q000494:pharmacology; D008969:Molecular Sequence Data; D009363:Neoplasm Proteins / Q000187:drug effects / Q000502:physiology*; D010911:Pituitary Neoplasms / Q000473:pathology*; D053284:Polyunsaturated Alkamides; D051381:Rats; D011960:Receptors, Estrogen / Q000187:drug effects / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis; D012045:Regulatory Sequences, Nucleic Acid; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014819:Vitellogenins / Q000235:genetics
chemical_list: D016895:Culture Media, Serum-Free; D007328:Insulin; D009363:Neoplasm Proteins; D053284:Polyunsaturated Alkamides; D011960:Receptors, Estrogen; D011993:Recombinant Fusion Proteins; D014819:Vitellogenins; D000077267:Fulvestrant; D004958:Estradiol; D007334:Insulin-Like Growth Factor I; C051781:ICI 164384