Three different thyroid hormone receptor isoforms are detected in a pure culture of ovine oligodendrocytes

Abstract

Thyroid hormones are important for the normal development of the central nervous system. In humans, the period around the end of the intrauterine life and the first few months of neonatal life is critically dependent on the presence of normal amounts of thyroid hormone. There are significant events occurring during this time; myelination is one. Myelin is synthesized by oligodendrocytes. A panel of site-specific polyclonal antibodies against alpha-1 thyroid hormone receptor (TR), alpha-2 variant TR, and beta-1 TR isoforms has been employed to investigate the presence of TR isoforms in a pure culture of ovine oligodendrocytes by the avidin-biotin peroxidase immunocytochemical method. Strong nuclear staining was obtained with all the anti-TR antibodies; no reaction products were detected in the cytoplasm or cellular processes. By contrast, an anti-myelin basic protein antibody gave strong cytoplasmic and process staining; no nuclear staining was seen. These latter results served to 1) confirm that the cells under study are oligodendrocytes; and 2) prove that the nuclear staining with anti-TR antibodies is specific. Preimmune sera were totally negative. Scatchard analysis of [125I] T3 binding by isolated oligodendrocyte nuclei demonstrated the existence of high-affinity--low-capacity T3 binding sites with a Ka of approximately 6 x 10(-9) M and a maximal binding capacity of approximately 20 fmol/100 micrograms of DNA. Our results demonstrate that differentiated oligodendrocytes express alpha-1 and alpha-2 variant and beta-1 isoforms of TR at the protein level and support the notion of a direct impact of thyroid hormones on oligodendrocytes in their regulation of myelin synthesis.

Transcriptional control in myelinating glia: Flavors and spices

“…Most of the literature on nuclear receptors in glia has so far been concerned with cataloguing. As evident from (Barres et al, 1994;Fierro-Renoy et al, 1995) Constitutive in culture, downregulated in mature cells (Barakat-Walter et al, 1993) RAR RAR␣ constitutive, RAR␤ inducible, RAR␥ - (Laeng et al, 1994) Not analyzed PPAR PPAR␦ϩ, PPAR␥Ϫ (Granneman et al, 1998) PPAR␦ high levels, PPAR␥ low levels (Granneman et al, 1998) GR, glucocorticoid receptor, MR, mineralocorticoid receptor; AR, androgen receptor; PR, progesterone receptor; ER, estrogen receptor; TR, thyroid hormone receptor; RAR, retinoic acid receptor; PPAR, peroxisome proliferator-activated receptor.…”

Growth Factor Control of CNS Myelination

“…Recent work has shown that T 3 blocks proliferation of OPCs and induces their differentiation [Baas et al, 1997]. Studies have determined that three T 3 receptor isoforms are expressed in the oligodendrocyte lineage: · 1 , · 2 , and ß 1 [Fiero-Renoy et al, 1995]. Interestingly, T 3 receptors · 1 and · 2 are expressed in both OPCs and differentiated oligodendrocytes, but the T 3 receptor ß 1 is only expressed in differentiated oligodendrocytes [Baas et al, 1998;Carre et al, 1998].…”

The challenge of understanding cerebral white matter injury in the premature infant

“…Both developing and mature oligodendrocytes express thyroid hormone receptors (Yusta et al, 1988, Fierro-Renoy et al, 1995, Baas et al, 2002). There appears to be sequential expression of the TRα and TRβ gene products such that all oligodendrocytes express the alpha receptors but only mature oligodendrocytes express the beta receptors (Baas et al, 1994, Carre et al, 1998).…”