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Endocrinology, doi:10.1210/endo-120-2-537
Endocrinology Vol. 120, No. 2 537-543
Copyright © 1987 by the Endocrine Society.
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Epidermal Growth Factor Decreases Thyroid Hormone Receptors and Attenuates Thyroid Hormone Responses in GH4C1 Cells*

HIDESUKE KAJI{dagger} and PATRICIA M. HINKLE{ddagger}

Department of Pharmacology and the Cancer Center, University of Rochester School of Medicine and Dentistry Rochester, New York 14642

Address requests for reprints to: Dr. Patricia M. Hinkle, Department of Pharmacology, University of Rochester, 601 Elmwood Avenue, Rochester, New York 14642.

Abstract

The present study was undertaken to examine the effect of long term exposure to epidermal growth factor (EGF) on thyroid hormone responses as well as the concentration of specific nuclear thyroid hormone receptors in GH4C1 rat pituitary tumor cells. GH4C1 cells were first incubated for 48 h in medium with 5% fetal calf serum depleted of thyroid hormones by ion exchange resin. EGF had no effect on thyroid hormone receptors after 2 h, but decreased [125I]T3 binding to 56% of control values at 24 h and 68% at 48 h. L-T3 (0.5 nM) caused down-regulation of thyroid hormone receptors, and addition of EGF caused a further decrease. T3 alone (0.5 nM) caused a 2- to 3-fold induction of GH after 48 h, and GH induction was significantly inhibited by the addition of 10 nM EGF. Scatchard analysis of specific nuclear [125I]T3 binding showed that 48-h incubation with 10 nM EGF decreased T3 receptors from a Bmax of 2.35 to 1.26 pmol/mg DNA in thyroid hormone-depleted medium without affecting receptor affinity (Kd, 80 pM). The decrease in nuclear thyroid hormone receptors caused by EGF was dose dependent, with half-maximal inhibition at 0.10 nM EGF. EGF attenuated the GH response to T3 with similar dose-response characteristics. When cells were incubated for 48 h with different concentrations of T3) EGF (10 nM) decreased thyroid hormone receptors to 56-72% of control values regardless of the dose of T3, and EGF shifted the ED50 for T3 stimulation of GH from 0.1 to 1.2 nM. EGF also reduced from 5- to 1.8-fold the increase in cell number caused by thyroid hormone over 2 weeks. In contrast, EGF stimulation of PRL synthesis was changed only slightly by thyroid hormone at all times. In conclusion, we demonstrate that low concentrations of EGF decrease nuclear thyroid hormone receptors and thyroid hormone responses; this may be the mechanism by which EGF suppresses T3-induced GH production in GH4C1 cells. (Endocrinology 120: 537–543, 1987)

Footnotes

* This work was supported in part by a grant from the NIH (AM 32847), Cancer Center Core Research Grant 11198, and funds received from The James P. Wilmot Fund.

{dagger} Wilmot Cancer Research Fellow.

{ddagger} Recipient of a Research Career Development Award (AM/NS-00827).

Received May 28, 1986.






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Copyright © 1987 by The Endocrine Society