Thyroid hormone and glucocorticoid regulation of receptor and target gene mRNAs in pituitary GH3 cells.
We have examined the effects of triiodothyronine (T3), in dose-response and time-course studies, on T3 receptor (T3R) alpha and beta and glucocorticoid receptor (GR) mRNAs in rate pituitary GH3 cells, in parallel with T3 actions on expression of the growth hormone (GH) target gene. Modulatory influences of dexamethasone (dex) on T3 action were studied by treatment with dex before and during T3 treatment. T3 treatment (1-100 nM) for 24 h reduced T3R alpha mRNA, while the presence of dex (1 microM) enhanced the T3 effect on T3R alpha mRNA and induced T3 inhibition of T3R beta mRNA. Stimulatory effects of T3 treatment on GH mRNA and release were seen in the face of inhibition of T3R mRNAs; these effects on GH were also enhanced by the presence of dex. T3 treatment for 24 h increased GR mRNA; this effect was inhibited by the presence of dex. We next examined the influence of dex on GR and T3R alpha and beta mRNAs, in parallel with effects of dex on the prolactin (PRL) target gene. Modulatory influences of T3 on dex action were studied by treatment of cells with T3 before and during dex treatment. Treatment with dex (0.1-10 microM) for 24 h reduced GR mRNA, an action enhanced by the presence of T3 (100 nM). Dex treatment resulted in inhibition of PRL mRNA and release despite parallel inhibition of GR mRNA by dex; these effects were enhanced by the presence of T3. In contrast to actions on GR, dex has no effect on T3R mRNAs. These effects of T3 and dex on receptor mRNAs suggest that glucocorticoid modulation of T3 action is not related to direct actions on T3R synthesis. In contrast, the mechanism of T3 modulation of glucocorticoid action may be due in part to alteration of GR mRNA expression. Effects of T3 and dex on target gene expression were observed in the presence of parallel reduction of their respective receptor mRNAs. This provides new evidence that interactions between these hormones are likely to be mediated by mechanisms other than regulation of receptor gene expression.
Williams
G R
GR
Department of Medicine, University of Birmingham, Queen Elizabeth Hospital, Edgbaston, U.K.
Franklyn
J A
JA
Sheppard
M C
MC
D000818:Animals; D015152:Blotting, Northern; D002478:Cells, Cultured; D003907:Dexamethasone / Q000494:pharmacology; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics / Q000378:metabolism; D010902:Pituitary Gland / Q000166:cytology / Q000378:metabolism*; D011388:Prolactin / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism*; D011988:Receptors, Thyroid Hormone / Q000235:genetics / Q000378:metabolism*; D014284:Triiodothyronine / Q000502:physiology*
D012333:RNA, Messenger; D011965:Receptors, Glucocorticoid; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D003907:Dexamethasone; D011388:Prolactin; D013006:Growth Hormone