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Tamoxifen Enhances the Sensitivity of Dispersed Prolactin-Secreting Pituitary Tumor Cells to Dopamine and Bromocriptine

Departments of Medicine (III) and Clinical Endocrinology, Erasmus University Rotterdam the Netherlands;
The Department of Medicine, Division of Endocrinology, University of Virginia School of Medicine Charlottesville, Virginia 22904

Address requests for reprints to: Dr. S. W. J. Lamberts, Department of Medicine III, University Hospital Dijkzigt, 40 Molewaterplein, 3015 GD Rotterdam, the Netherlands.

Abstract

The administration of bromocriptine to rats bearing the estrogen-induced PRL-secreting pituitary tumor 7315a was previously shown to be without effect on tumor growth and serum PRL. In the present study the sensitivity of trypsindispersed cell suspensions prepared from this pituitary tumor to dopamine, bromocriptine, and TRH was investigated. PRL secretion by these cells showed a decreased sensitivity to dopamine; 0.1 and 0.5 µM dopamine were without effect, while 1 µM dopamine suppressed PRL secretion by 25%. This suppressing effect could be prevented by haloperidol (50 nM). Bromocriptine (0.5 µM) suppressed PRL secretion by 25%, while 0.1 µM was without effect.

The antiestrogenic compound tamoxifen (0.1–1.0 µM) was without effect on PRL secretion by dispersed pituitary tumor cells in vitro, but 0.1 and 1 µM tamoxifen made these cells twice as sensitive to dopamine and 5 times as sensitive to bromocriptine, respectively. The enhancing effect of tamoxifen on the sensitivity of these tumor cells to bromocriptine could be prevented by coincubation with 1 nM 17β-estradiol. Tamoxifen (1 µM) prevented the positive effect of TRH on PRL secretion completely.

Pituitary tumor formation induced by estrogens in the rat is accompanied and/or characterized by a loss of sensitivity of PRL secretion to dopamine by the tumor both in vivo and in vitro. The addition of the antiestrogenic compound tamoxifen to dispersed tumor cells partly restored the sensitivity of PRL secretion to dopamine and bromocripfcine and prevented the effect of TRH. This effect of tamoxifen occurred within 2.5–4 h and could be prevented by coincubation with 17β-estradiol. (Endocrinology 106: 702, 1980)

Footnotes

^* On leave from the Department of Physiology, University de los Andes, Merida, Venezuela.

Received June 20, 1979.

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