Immunofluorescent localization of thyroid hormone receptor isoforms in glial cells of rat brain.
The three currently recognized T3 binding thyroid hormone receptor (TR) isoforms, TR alpha 1, TR beta 1, and TR beta 2, arise from two distinct genes (alpha and beta), whereas two closely related non-T3-binding receptor variants, collectively designated TR alpha 2, arise from alternate splicing of the alpha gene transcript. Using a panel of specific antisera to these isoforms we have assessed the presence or absence of TRs in oligodendrocytes and astrocytes of rat cerebrum and cerebellum. Inferences as to colocalization of the receptor isoforms and cell-specific marker proteins were based on immunohistochemical analysis of the differential emissions of paired immunofluorescent probes. Antisera against myelin basic protein (MBP) identified oligodendroglia, and glial fibrillary acidic protein identified astrocytes. MBP-positive oligodendrocytes displayed positive fluorescent signals with each of the three TR isoform-specific antisera and the antiserum to the receptor variants. These findings are consistent with the concept that the MBP gene is a direct target for thyroid hormone action. TR immunoreactivity appeared to localize primarily to the nuclei of these cells. In contrast, we observed no immunofluorescent signals for any of the TR isoforms in glial fibrillary acidic protein-positive astrocytes. These findings raise the possibility that any effect of thyroid hormone on astrocyte function and structure is mediated indirectly as a result of interaction of thyroid hormone with receptors situated in nonastrocyte cells or as a result of nonnuclear mechanisms.
Carlson
D J
DJ
Department of Medicine, University of Minnesota, Minneapolis 55455.
Strait
K A
KA
Schwartz
H L
HL
Oppenheimer
J H
JH
D000818:Animals; D001253:Astrocytes / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D001923:Brain Chemistry; D005455:Fluorescent Antibody Technique; D007150:Immunohistochemistry; D007536:Isomerism; D008297:Male; D004676:Myelin Basic Protein / Q000032:analysis; D009457:Neuroglia / Q000737:chemistry* / Q000166:cytology* / Q000648:ultrastructure; D009836:Oligodendroglia / Q000737:chemistry / Q000166:cytology / Q000648:ultrastructure; D051381:Rats; D017207:Rats, Sprague-Dawley; D011988:Receptors, Thyroid Hormone / Q000032:analysis*
D004676:Myelin Basic Protein; D011988:Receptors, Thyroid Hormone