Interaction between insulin and thyroid hormone in rat pituitary tumour cells: insulin attenuates tri-iodothyronine-induced growth hormone mRNA levels.
Insulin has previously been shown to inhibit basal and stimulated rat GH (rGH) secretion as well as basal GH transcription in rat pituitary cells. The effect of physiological doses of insulin on tri-iodothyronine (T3)-stimulated GH mRNA levels in rat pituitary tumour cells was therefore examined. Insulin (7 nmol/l) suppressed T3-stimulated GH mRNA levels in GC and GH3 rat pituitary tumour cells by 58%. This inhibitory effect of insulin on T3-stimulated GH mRNA levels was already present after 24 h of treatment, and persisted for at least 48 h after insulin treatment was withdrawn. The effect of insulin on GH mRNA was selective, as rat prolactin mRNA was stimulated by insulin and T3 in the same cells. Treatment of cells with cycloheximide (10 mumol/l) did not alter the attenuation of GH mRNA levels by insulin, indicating that the insulin effect is independent of new protein synthesis. When de-novo mRNA synthesis was blocked with actinomycin D (4 micrograms/ml) for up to 7 h, an additional decrease in the relative amount of GH mRNA levels was observed after 24, 48 and 72 h of insulin treatment, indicating that an effect of insulin on GH mRNA stability is likely. The results show that physiological doses of insulin selectively attenuate the stimulatory effect of T3 on GH mRNA levels. This suppressive effect of insulin occurs independently of protein synthesis and is presumably mediated both at a transcriptional and post-transcriptional level.
Department of Medicine, Cedars-Sinai Medical Center-UCLA School of Medicine 90048.
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Prager
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Weber
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Gebremedhin
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Melmed
D000818:Animals; D003513:Cycloheximide / Q000494:pharmacology; D003609:Dactinomycin / Q000494:pharmacology; D005786:Gene Expression Regulation; D013006:Growth Hormone / Q000235:genetics*; D007328:Insulin / Q000494:pharmacology*; D010902:Pituitary Gland / Q000187:drug effects / Q000502:physiology*; D010911:Pituitary Neoplasms; D011388:Prolactin / Q000235:genetics; D012333:RNA, Messenger / Q000032:analysis*; D051381:Rats; D013997:Time Factors; D014284:Triiodothyronine / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D007328:Insulin; D012333:RNA, Messenger; D014284:Triiodothyronine; D003609:Dactinomycin; D011388:Prolactin; D013006:Growth Hormone; D003513:Cycloheximide