Insulin-like growth factor-I action on hypothyroid XXXX pituitary cells: suppression of triiodothyronine-induced growth hormone secretion and messenger ribonucleic acid levels.

@entity1 @entity1375 @entity7750 @entity442 @entity2135 @entity35
T3 stimulates in vitro GH secretion, whereas @entity7750 have been shown to suppress GH. We, therefore, tested the effects of a recombinant @entity1 @entity442 ; Thr 59) on T3-induced GH secretion. Pituitary monolayer cultures were derived from 4- to 7-week surgically thyroidectomized male @entity35 and grown in hypothyroid medium stripped of T3 and T4. @entity1375 pituitary cell monolayers secreted low levels of GH (200 ng/ml X 72 h). GH secretion was stimulated (185% of T3-free controls) by the addition of T3 (0.1 nM) during 48 h of incubation. @entity2135 (up to 13 nM) did not alter basal GH secretion, but inhibited the induction of GH by T3. @entity2135 (0.65 nM) suppressed the 3.5-fold induction of GH by 0.25 nM T3 by 35% (p less than 0.001), whereas maximal (68%) GH suppression was seen with 6.5 nM @entity2135 (p less than 0.001). The inhibition of T3-induced GH by @entity2135 occurred after 24 h. By 72 h, @entity2135 (3.25 nM) suppressed GH stimulation by up to 1 nM T3 [213 +/- 12 (+/- SE) vs. 88 +/- 8 ng GH/10(4) cells]. Insulin, epidermal growth factor, and fibroblast growth factor did not alter the T3-induced GH secretion. GH mRNA was measured by agarose gel blot hybridization analysis and nitrocellulose dot blot hybridization of cytoplasmic RNA with @entity35 GH [32P]cDNA. T3 (0.25 nM) stimulated the hybridization of immobilized pituitary cell RNA extracts, indicating an almost 3-fold increase in @entity35 (r) GH mRNA levels; @entity2135 (3.25 nM) suppressed the T3-induced rGH mRNA content of pituitary cells from thyroidectomized @entity35 by 50% during 72 h of incubation. Maximal suppression of rGH mRNA induced by 0.25 nM T3 was achieved with 6.5 nM @entity2135 (35% of T3-treated cells). These results show that @entity2135 does not alter low basal GH secretion in pituitary cells from hypothyroid @entity35 . @entity2135 does, however, block the T3-induction of GH secretion and suppresses GH mRNA levels stimulated by T3. As T3 is known to directly stimulate GH gene transcription, @entity2135 may suppress T3 action on GH at a posttranscriptional site.
