Rapid actions of Triiodothyronine (T3) on TSH expression and secretion: new mechanisms involved in the negative feedback.

• Grant number: 09/17813-9
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: May 01, 2010
• End date: February 28, 2015
• Field of knowledge: Biological Sciences - Physiology - General Physiology
• Principal Investigator: Maria Tereza Nunes
• Grantee: Paula Bargi de Souza
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated scholarship(s): 12/06643-8 - Rapid actions of triiodothyronine (T3) on intracellular calcium and membrane potential of thyrotrophs and implications on TSH secretion, BE.EP.DR

Abstract

Thyroid hormone (TH) exerts effects on metabolism, growth and development, by means of its interaction to nuclear receptors (TRs) bound to the promoter regions of its target genes, mechanism by which it induces or inhibit their expression. These actions are known as genomic actions, ant take 1 - 2 h to be elicited. However, some TH actions are triggered in a short period of time (seconds to minutes), even in the presence of transcription gene inhibitors, which indicates that TH could also exert some non genomic actions.TH synthesis and secretion are regulated by the pituitary hormone thyrotropin (TSH), whose secretion is under control of the thyrotropin-releasing hormone (TRH), produced in the hypothalamus. Moreover, the activity of the hypothalamic-pituitary system is regulated by TH plasma concentration through a negative feedback mechanism, in which TH reduces the synthesis and secretion of TSH and TRH.Whereas several studies have been conducted to better understand the mechanism by which TH acts suppressing TSH gene expression, there are few about its possible non-genomic actions on the control of TSH gene expression. Studies developed in our laboratory demonstrated that hypothyroid rats acutely treated with T3 (30 min) present alterations in BTSH mRNA expression and polyadenylation, as well as in the pituitary TSH content; these changes occurred concomitantly with a marked decrease in TSH in the periphery of thyrotrophs, indicating a possible nongenomic action of T3 on TSH synthesis and secretion.The present study aimed to characterize these non-genomic actions of T3 on BTSH processing in TaT1 cell culture by evaluating BTSH mRNA expression, decay rate and polyadenylation, as well as BTSH mRNA interaction to cytosolic proteins and polysomes and the pituitary TSH content. We will further investigate the effects of the acute T3 administration on TSH labeling and actin polymerization of thyrotropes.

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

BARGI-SOUZA, P.; GOULART-SILVA, F.; NUNES, M. T.. Novel aspects of T-3 actions on GH and TSH synthesis and secretion: physiological implications. JOURNAL OF MOLECULAR ENDOCRINOLOGY, v. 59, n. 4, p. R166-R177, NOV 2017. (14/25888-7, 12/06643-8, 09/17813-9, 13/05629-4)

BARGI-SOUZA, PAULA; GOULART-SILVA, FRANCEMILSON; NUNES, MARIA TEREZA. Posttranscriptional actions of triiodothyronine on Tshb expression in T alpha T1 cells: New insights into molecular mechanisms of negative feedback. Molecular and Cellular Endocrinology, v. 478, p. 45-52, DEC 15 2018. (13/05629-4, 09/17813-9, 14/25888-7)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

SOUZA, Paula Bargi de. Rapid actions of triiodothyronine (T3) on TSH expression and secretion: new mechanisms involved in the negative feedback.. 2015. Doctoral Thesis - Universidade de São Paulo (USP). Instituto de Ciências Biomédicas (ICB/SDI) São Paulo.