Loss of Basal and TRH-StimulatedTshbExpression in Dispersed Pituitary Cells

Abstract

This study addresses the in vivo and in vitro expression pattern of three genes that are operative in the thyrotroph subpopulation of anterior pituitary cells: glycoprotein α-chain (Cga), thyroid-stimulating hormone β-chain (Tshb), and TRH receptor (Trhr). In vivo, the expression of Cga and Tshb was robust, whereas the expression of Trhr was low. In cultured pituitary cells, there was a progressive decline in the expression of Cga, Tshb, and Trhr. The expression of Tshb could not be reversed via pulsatile or continuous TRH application in variable concentrations and treatment duration or by the removal of thyroid and steroid hormones from the sera. In parallel, the expression of CGA and TSHB proteins declined progressively in pituitary cells from both sexes. The lack of the effect of TRH on Tshb expression was not related to the age of pituitary cultures and the presence of functional TRH receptors. In cultured pituitary fragments, there was also a rapid decline in expression of these genes, but TRH was able to induce transient Tshb expression. In vivo, thyrotrophs were often in close proximity to each other and to somatotroph and folliculostellate cell networks and especially to the lactotroph cell network; such an organization pattern was lost in vitro. These observations suggest that the lack of influence of anterior pituitary architecture and/or intrapituitary factors probably accounts for the loss of basal and TRH-stimulated Tshb expression in dispersed pituitary cells.

Calcium signaling properties of a thyrotroph cell line, mouse TαT1 cells

“…Such uncoupling, however, is not unique for these cells; the lack of the effect of TRH on Tshb expression was also observed in dispersed rat pituitary cells [3]. This observation reinforces the hypothesis that influence of other cell types and/or extracellular matrix proteins is/are needed for TRH-induced Tshb expression, which is commonly observed in vivo [50, 51].…”

“…Within the lobule, five secretory cells are not randomly distributed but are organized with specific topographical affinities. For example, thyrotrophs are in close proximity with somatotrophs and especially with lactotrophs [3]. Folliculostellate cells are located in the center of lobule and form an excitable network that signals through gap junctions [4].…”

“…Ashworth and Hinkle showed that thyrotropin-releasing hormone (TRH) caused increase in intracellular calcium concentration ([Ca 2+ ] i ) in individual rat thyrotrophs and that the pattern of response was heterogeneous, as well as that potassium-induced depolarization of cells leads to increase in [Ca 2+ ] i , indicating the presence of voltage-gated calcium (Ca v ) channels [24]. We also observed variable patterns of TRH-induced calcium signaling in identified thyrotrophs [3] as well as their spontaneous firing of action potentials (APs) [25]. …”

New insights into thyroid hormone action

“…TRH released into the median eminence acts on the TRH-receptor located in the membrane of thyrotrophs, the TSH-producing cell in the pituitary. Thyrotrophs lose their ability to secrete TSH when disaggregated in cell culture, suggesting a functional role for the architecture of the anterior hypophysis of the pituitary and the possible participation of other signaling factors to modulate thyrotroph sensitivity to TRH in vivo (Bargi-Souza et al, 2015). The HPT axis plays the major role in maintaining the homeostasis of circulating TH levels as circulating T4 and T3 feed back to both the hypothalamus and the pituitary to regulate TRH and TSH production (see Negative Regulation by Thyroid Hormone).…”

Avaliação dos efeitos agudos e em longo prazo do hormônio tireoidiano sobre o eixo hipotálamo-hipófise-adrenal e sua importância fisiológica.

“…Outros trabalhos já verificaram a presença do receptor de TSH (TSHR) na hipófise de humanos, mais particularmente nas células folículo estreladas (PRUMMEL et al, 2000) e na hipófise do rato (BROKKEN et al, 2001). Mesmo com essas informações confirmamos a expressão do RNAm do TSHR, já que a expressão de alguns genes pode se encontrar alterada pelo processo de dissociação do tecido hipofisário (BARGI-SOUZA et al, 2015). Em relação ao TRH, não houve alterações na secreção de ACTH quando as células hipofisárias foram tratadas com este hormônio, já o TSH promoveu aumento de secreção de ACTH pelos corticotrofos.…”