Rapid actions of triiodothyronine (T3) on intracellular calcium and membrane potential of thyrotrophs and implications on TSH secretion

• Grant number: 12/06643-8
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: October 01, 2012
• End date: July 31, 2013
• Field of knowledge: Biological Sciences - Physiology - Physiology of Organs and Systems
• Principal Investigator: Maria Tereza Nunes
• Grantee: Paula Bargi de Souza
• Supervisor: Stanko S. Stojilkovic
• Host Institution: Instituto de Ciências Biomédicas (ICB). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Institution abroad: National Institutes of Health, Bethesda (NIH), United States
• Associated to the scholarship: 09/17813-9 - Rapid actions of Triiodothyronine (T3) on TSH expression and secretion: new mechanisms involved in the negative feedback., BP.DR

Abstract

In the last few years, the number of evidences demonstrating the importance of rapid actions triggered by thyroid hormones (TH) on stability and translation of several proteins has increased, actions which are independent of the gene transcription process.Both synthesis and secretion of THs are regulated by thyrotropin (TSH), whose synthesis and secretion are under the control of thyrotropin release hormone (TRH) and THs by means of a negative feedback mechanism in the pituitary and hypothalamus.It is known that the thyrotrophs, which are pituitary cells that produce and release TSH, are able to fire action potentials, which are directly related to alterations on intracellular calcium concentration and consequently to the TSH secretion.Considering the data obtained in our laboratory which show that triiodothyronine (T3) administered acutely (30 min) to hypothyroid rats increases the TSH protein content in the pituitary and reduces the TSH labeling on areas close to plasma membrane. Therefore, we suggest that T3 could exert a rapid inhibitory effect on TSH secretion.Thus, the present project aims to characterize non genomic actions of T3 on the pattern of TSH secretion in thyrotrophs of primary culture of pituitary and/or in TalphaT1 cells, as well as the possible alterations on spontaneous electrical activity, cyclic nucleotide production and calcium signaling which are directly related to exocytosis process. Our proposal is to develop this project in Ph. D. Stanko S. Stojilkovics laboratory in the National Institutes of Health (Bethesda, Maryland, EUA), whose research is centered on the investigation of calcium signaling pathways at the cellular and molecular levels, and determination of the manner in which hormones and neurotransmitters utilize calcium as an intracellular messenger in neuroendocrine cells. His current investigations are in accordance with our goals to understand the mechanism which quickly reduces TSH secretion by possible non genomic actions of T3, given that these effects could be involved with the calcium signaling. (AU)

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)

TOMIC, MELANIJA; BARGI-SOUZA, PAULA; LEIVA-SALCEDO, ELIAS; NUNES, MARIA TEREZA; STOJILKOVIC, STANKO S.. Calcium signaling properties of a thyrotroph cell line, mouse T alpha T1 cells. Cell Calcium, v. 58, n. 6, p. 598-605, DEC 2015. (13/05629-4, 12/06643-8)

BARGI-SOUZA, PAULA; KUCKA, MAREK; BJELOBABA, IVANA; TOMIC, MELANIJA; JANJIC, MARIJA M.; NUNES, MARIA TEREZA; STOJILKOVIC, STANKO S.. Loss of Basal and TRH-Stimulated Tshb Expression in Dispersed Pituitary Cells. Endocrinology, v. 156, n. 1, p. 242-254, JAN 2015. (12/06643-8)

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)