TSH is the main regulator of the thyroid hormones (THs) synthesis/secretion, which in turn exert a negative feedback mechanism on the Tshb mRNA expression in the pituitary gland by reducing their transcription rate. Some of triiodothyronine (T3) effects are also shown in short period of time, characterizing the non genomic actions of THs. It has been shown previously that T3 acts on posttranscriptional steps of TSH synthesis and reduces its secretion when acutely administered to hypothyroid rats. The present study aimed to: i) characterize the pathways involved in the rapid inhibition of the TSH secretion induced by T3 in primary cultures of anterior pituitary cells and ii) evaluate the participation of T3 on calcium and magnesium intracellular mobilization in slices of pituitary of hypothyroid rats. The cultured plates were treated with three different stimuli, RGD (100 μg/ml 50 min), Wortmannin (1 μM 30 min), and EGTA (1 mM). Lately, T3 was added (10−8 M) for 30 min. Slices of pituitary were incubated with Fluo-4AM and Magnesium Green AM probes to address the mobilization of calcium and magnesium after T3 treatment. The results showed a rapid increase of TSHB content in intracellular extracts while the amount of TSH in extracellular media was reduced after T3 challenge. The treatment with RGD and Wortmannin abolished T3 effects. No alteration on TSH secretion induced by T3 was observed in the presence of EGTA in the culture media neither in calcium intracellular mobilisation, while intracellular concentration of magnesium was altered under the same condition T3 treatment (16% of pituitary cells). The Therefore, we propose the existence of an additional mechanism that decreases the TSH synthesis/secretion, triggered in few minutes by T3, through its interaction with αVβ3 integrin at the plasma membrane, featuring a non genomic action of this thyroid hormone on its own synthesis/secretion.
Disclosure: This work was supported by the FAPESP (São Paulo Research Foundation) (2009/17813-9).
16 - 20 May 2015
European Society of Endocrinology