Multiple Transduction Pathways Mediate Thyrotropin Receptor Signaling in Preosteoblast-Like Cells.

Multiple Transduction Pathways Mediate Thyrotropin Receptor Signaling in Preosteoblast-Like Cells. Endocrinology. 2016 Mar 7;:en20152040 Authors: Boutin A, Neumann S, Gershengorn MC Abstract It has been shown that the thyroid stimulating hormone (TSH) receptor (TSHR) couples to a number of different signaling pathways although the Gs-cAMP pathway has been considered primary. Herein we measured the effects of TSH on bone marker mRNA and protein expression in preosteoblast-like U2OS cells stably expressing TSHRs. We determined which signaling cascades are involved in the regulation of interleukin 11 (IL11), osteopontin (OPN), and alkaline phosphatase (ALPL). We demonstrated that TSH-induced upregulation of IL11 is primarily mediated via the Gs pathway as IL11 was upregulated by forskolin (FSK), an adenylyl cyclase activator, and inhibited by protein kinase A (PKA) inhibitor H-89 and by silencing of Gαs by siRNA. OPN levels were not affected by FSK, but its upregulation was inhibited by TSHR/Gi-uncoupling by pertussis toxin (PTX). PTX decreased p38 MAPK kinase phosphorylation, and a p38 inhibitor and siRNA knockdown of p38 alpha inhibited OPN induction by TSH. Upregulation of ALPL expression required high doses of TSH (EC50 395 nM) whereas low doses (EC50 19 nM) were inhibitory. FSK-stimulated cAMP production decreased basal ALPL expression whereas PKA inhibition by H-89 and silencing of Gαs increased basal levels of ALPL. Knockdown o...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research