The estrogenic and antiestrogenic properties of tamoxifen in GH4C1 pituitary tumor cells are gene specific.

Shull, James D.; Beams, Faith E.; Baldwin, Tonia; Gilchrist, Cindy A.; Hrbek, M

doi:10.1210/mend.6.4.1584221

Cited by 11 publications

(2 citation statements)

References 25 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Also in line with the possibility that anti-oestrogens interfere with growth factor action is the idea that although the oestrogen-liganded ERs might have no effect, the ERs liganded by anti-oestrogens could interfere with the ability of peptide-induced nuclear factors to activate tran¬ scription of growth-promoting genes. Although at present we cannot directly address this question for growth, for two oestrogen-regulated proteins, namely prolactin and the progesterone receptor (PR) (Shull et al 1992), the above would appear not to be the case. Therefore both prolactin secretion measured under conditions that reflect synthesis and PRs measured by the binding of the synthetic ligand R5020 are increased by OE2.…”

Section: Discussionmentioning

confidence: 95%

The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen

Newton

Trapp²,

Pagotto³

et al. 1994

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 95%

The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen

Newton

Trapp²,

Pagotto³

et al. 1994

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

show abstract

“…The mechanisms by which ligands for nuclear receptors exhibit both agonism and antagonism are not clear. Molecules exhibiting such a mixture of activities have been identified that act to antagonize the actions of ligands for many members of the nuclear receptor family, including androgens, estrogens, and progestins (12,(24)(25)(26)(27)(28). Detailed studies of the activities of such compounds have suggested models in which the receptor assumes distinct conformations that permit the liganded receptor to interact with the transcription apparatus in a productive or nonproductive fashion (29,30).…”

Section: Discussionmentioning

confidence: 99%

Functional Activities of the A and B Forms of the Human Androgen Receptor in Response to Androgen Receptor Agonists and Antagonists

Gao

McPhaul

1998

Molecular Endocrinology

View full text Add to dashboard Cite

The androgen receptor (AR) is present in many cells in two forms. The B form migrates with an apparent mass of 110 kDa and constitutes more than 80% of the immunoreactive receptor in most cell types. The A form of the AR migrates with an apparent mass of 87 kDa, appears to derive from internal translation initiation at methionine-188 in the AR open-reading frame, and usually constitutes 20% or less of the immunoreactive AR present. Previous experiments designed to examine the functional capacity of the A and B forms of the AR have been hampered by marked differences in the expression levels of the two isoforms, as the nucleotide sequence surrounding the codon encoding methionine-188 causes it to be used inefficiently as a translation initiation site. To circumvent this, we altered the nucleotide sequence surrounding methionine-188 to render it more similar to that surrounding the codon encoding methionine-1. Transfection of a cDNA containing these changes resulted in similar levels of expression of A and B forms of the AR as assessed by immunoblot assays using antibodies directed at an epitope preserved in both. Functional activities of these cDNAs were assessed using cotransfection assays that employed two model androgen-responsive genes (MMTV-luciferase and PRE2-tk-luciferase) in response to mibolerone, a potent androgen agonist, in three different cell lines. These studies demonstrated subtle differences in the activities of the A and B isoforms, which depended on the promoter and cell context. Additional studies failed to reveal any major differences in the responses of the AR-A and AR-B isoforms to a variety of androgen agonists and antagonists, suggesting that the previously reported functional defect of the AR-A is due principally to its level of expression. When assays of AR function are performed under conditions in which levels of expression of the two isoforms are equivalent, the AR-A and AR-B possess similar functional activities.

show abstract

An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain*1

McKenna

Simon

Cologer-Clifford

1992

Hormones and Behavior

View full text Add to dashboard Cite

The estrogenic and antiestrogenic properties of tamoxifen in GH4C1 pituitary tumor cells are gene specific.

Cited by 11 publications

References 25 publications

The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen

The oestrogen receptor modulates growth of pituitary tumour cells in the absence of exogenous oestrogen

Functional Activities of the A and B Forms of the Human Androgen Receptor in Response to Androgen Receptor Agonists and Antagonists

An assessment of agonist/antagonist effects of tamoxifen in the female mouse brain*1

Contact Info

Product

Resources

About