Thyroid Hormone Regulates the Extracellular Organization of Laminin on Astrocytes1

Abstract

Astrocytes produce laminin, a key extracellular matrix guidance molecule in the developing brain. Laminin is bound to transmembrane receptors on the surface of astrocytes known as integrins, which are, in turn, bound to the microfilament meshwork inside the astrocyte. Previous studies have shown that T4 regulates the pattern of integrin distribution in astrocytes by modulating the organization of the microfilaments. In this study, the effect of thyroid hormone on the secretion and topology of laminin in astrocytes was examined. Linear arrays of secreted laminin were observed on the surface of the T4-treated astrocytes within 10 h after seeding the cells onto poly-D-lysine-coated coverslips and became an organized meshwork by 24 h. In contrast, little if any laminin was identified on the surface of either hormone-deficient or T3-treated cells until 36 h after seeding and then was restricted to punctate deposits. Secretion of laminin into the medium by hormone-deficient and T3-treated cells was significantly greater than that by T4-treated cells. Conversely, deposition of laminin into the extracellular matrix was significantly greater in T4-treated cells than in hormone-deficient and T3-treated cells. Thyroid hormone had no effect on the production of laminin by astrocytes. These data show that T4 regulates the extracellular deposition and organization of laminin on the surface of astrocytes and provide a mechanism by which this morphogenic hormone can influence neuronal migration and axonal projection in the developing brain.

Neuritogenesis Induced by Thyroid Hormone-treated Astrocytes Is Mediated by Epidermal Growth Factor/Mitogen-activated Protein Kinase-Phosphatidylinositol 3-Kinase Pathways and Involves Modulation of Extracellular Matrix Proteins

“…Our data contrast with those obtained from Farwell and Dubord-Tomasetti (29), who demonstrated that T4 but not T3 increases laminin expression. We believe, however, that this apparent discrepancy between these two works most likely reflect fundamental differences in the technical approaches such as hormone treatment schedule, hormone concentration, and differences in culture conditions.…”

Stem Cells from Healthy and Tendinopathic Human Tendons: Morphology, Collagen and Cytokines Expression and Their Response to T3 Thyroid Hormone

“…The role of thyroid hormones (THs), T3 and thyroxine (T4), in the development and metabolism of many tissues and organs, both in early and adult life, is mainly mediated through T3, which regulates gene expression by binding to the TH receptors (TR)-α and -β [ 47 , 48 , 49 , 50 ]. Thyroid hormones have been reported to modulate cells morphology, differentiation, and proliferation, and to regulate ECM organization and synthesis also in tendon tissue [ 17 , 18 , 51 ].…”

Maternal hormonal milieu influence on fetal brain development

“…Thyroid hormone is required early in pregnancy for normal neurogenesis, neuronal migration, neuronal and glial cell differentiation, myelination, and synaptogenesis (Bernal, 2017;Eayrs, 1953;Lavado-Autric et al, 2003). In fact, thyroid hormones were shown to modify expression of genes associated with cell cycle and intracellular signaling (E2F1, p53, cyclins, and cyclin-dependent kinase inhibitors), cytoskeleton organization (actin and microtubule polymerization), and extracellular matrix contents (laminin, fibronectin, and several adhesion molecules), which are involved in neurogenesis and neuronal migration (Bernal, 2017;Farwell & Dubord-Tomasetti, 1999;Iglesias et al, 1996;Koibuchi, Jingu, Iwasaki, & Chin, 2003;Leonard & Farwell, 1997;Lin et al, 2004;). Neurogenin 2 and Reelin are also proteins involved in neuron development and neuronal migration which expression has also been proven to be modulated by thyroid hormones (Dong et al, 2009;Pathak, Sinha, Mohan, Mitra, & Godbole, 2011).…”