Abstract
There is increasing experimental evidence of the nongenomic action of thyroid hormones mediated by receptors located in the plasma membrane or inside cells. The aim of this work was to characterize the reverse T3 (rT3) action on calcium uptake and its involvement in immature rat Sertoli cell secretion. The results presented herein show that very low concentrations of rT3 are able to increase calcium uptake after 1 min of exposure. The implication of T-type voltage-dependent calcium channels and chloride channels in the effect of rT3 was evidenced using flunarizine and 9-anthracene, respectively. Also, the rT3-induced calcium uptake was blocked in the presence of the RGD peptide (an inhibitor of integrin-ligand interactions). Therefore, our findings suggest that calcium uptake stimulated by rT3 may be mediated by integrin αvβ3. In addition, it was demonstrated that calcium uptake stimulated by rT3 is PKC and ERK-dependent. Furthermore, the outcomes indicate that rT3 also stimulates cellular secretion since the cells manifested a loss of fluorescence after 4 min incubation, indicating an exocytic quinacrine release that seems to be mediated by the integrin receptor. These findings indicate that rT3 modulates the calcium entry and cellular secretion, which might play a role in the regulation of a plethora of intracellular processes involved in male reproductive physiology.
Highlights
Thyroid hormones (THs) are iodinated compounds known to influence gene expression in virtually every vertebrate cell
Since these results clearly show that T4, T3 and reverse T3 (rT3) specificity for rapid responses in testis or Sertoli cells are quite different, in this study we investigated the involvement of integrin on calcium uptake and exocytosis triggered by rT3 in immature rat Sertoli cells
In this study we investigated the rapid action of rT3 in 11-dayold rat Sertoli cells using the radioisotope 45Ca2+, an accurate approach to measuring rapid effects on the plasma membrane
Summary
Thyroid hormones (THs) are iodinated compounds known to influence gene expression in virtually every vertebrate cell. THs action is critically important for development, tissue differentiation, and maintenance of metabolic balance in mammals. Thyroxine (3,5,3’,5’-L-tetraiodothyronine; T4) is known to be the main secretory product of the thyroid gland in all vertebrates, and can be activated to triiodothyronine (3,5,3’triiodothyronine; T3) in a stage- and tissue-specific manner by phenolic ring deiodination (outer ring deiodination) catalyzed by two iodothyronine deiodinases, D1 and D2. D1, D2, and D3, are expressed in testis at different levels from weanling to adult life, D3 activity predominates in the developmental period and declines in adult life [3]. The presence of specific nuclear thyroid hormone receptors (TRs), described in prepubertal Sertoli cells, implies the existence of an early and critical influence of thyroid hormones on testis development [4]. Alterations in thyroid activity are frequently associated with changes in male reproductive functions, since hypothyroidism is associated with a marked delay in sexual maturation and development [5]
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