Reciprocal regulation of preprothyrotropin-releasing hormone (TRH) mRNA in the rat anterior hypothalamus by thyroid hormone: dissociation from TRH concentrations during hypothyroidism.

TRH mRNA has not been quantified concomitantly with TRH itself to examine graded effects of thyroid hormones (TH) upon TRH gene transcriptional regulation and post-transcriptional expression. To examine such TH effects, rats were rendered thyrotoxic with L-T3 (50 micrograms per 100g body weight) or hypothyroid by total thyroidectomy. After decapitation, frozen coronal brain sections were prepared in a matrix for hypothalamic micropunches. PreProTRH mRNA was quantified in punch pools by slot-blot hybridization and densitometry, using a 32P 1.2Kb rat riboprobe (gift of Drs. S. Lee and R. Goodman). T3 toxicosis resulted in parallel reductions in PreProTRH mRNA (-45%) and TRH concentrations determined by RIA (-43%), 1.1 versus 1.9 ng/mg protein, p less than 0.01. Conversely, elevations in PreProTRH mRNA were stimulated by hypothyroidism on Day 14 (+32%). However, TRH concentrations were reduced paradoxically from 2.2 +/- 0.05 ng/mg protein to 0.68 +/- 0.03, p less than 0.01. No changes, in contrast, were identified in whole hypothalamic extracts in either PreProTRH mRNA or TRH after T3 treatment. It is concluded that TH do exert inhibitory effects upon PreProTRH mRNA transcription, and in the specific hypothalamic nucleus concerned with thyroid regulation (PVN). The failure of TRH concentrations to rise concordantly with activated TRH gene transcription in hypothyroidism suggests that TH may exert inhibitory effects upon PreProTRH mRNA translation, in addition to inhibition of TRH gene transcription and TRH secretion.