Epidermal growth factor decreases thyroid hormone receptors and attenuates thyroid hormone responses in GH4C1 cells.
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.
D000818:Animals; D002460:Cell Line; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000494:pharmacology*; D007700:Kinetics; D010911:Pituitary Neoplasms / Q000378:metabolism; D051381:Rats; D011988:Receptors, Thyroid Hormone / Q000187:drug effects / Q000378:metabolism*; D014284:Triiodothyronine / Q000378:metabolism / Q000494:pharmacology*
D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D004815:Epidermal Growth Factor