Increased beta(2)-adrenergic receptor activity by thyroid hormone possibly leads to differentiation and maturation of astrocytes in culture.
(1) Our earlier studies indicate a downsteam regulatory role of the beta-adrenergic receptor (beta-AR) system in thyroid hormone induced differentiation and maturation of astrocytes. In the present study we have investigated the contributions of the subtypes of beta-AR in the above phenomenon. (2) Primary astrocyte cultures were grown under thyroid hormone deficient as well as under euthyroid conditions. [(125)I]Pindolol ([(125)I]PIN) binding studies showed a gradual increase in the specific binding to beta(2)-AR when observed at 5, 10, 15, and 20 days under both cultural conditions. Thyroid hormone caused an increase in binding of [(125)I]PIN to beta(2)-AR compared to thyroid hormone deficient controls at all ages of astrocyte culture. (3) Saturation studies using [(125)I]PIN in astrocyte membranes prepared from 20-day-old cultures showed a significant increase in the affinity of the receptors (K (D)) in the thyroid hormone treated cells without any change in receptor number (B (max)). (4) beta(2)-AR mRNA levels were measured by real-time PCR during ontogenic development as well as during exposure of 10-day-old hypothyroid cultures to normal levels of thyroid hormone for 2, 6, 12, and 24 h. None of the conditions caused any significant change in the beta(2)-adrenergic receptor mRNA levels when compared with corresponding hypothyroid controls. (5) Over expression of beta(2)-AR cDNA in hypothyroid astrocytes caused morphological transformation in spite of the absence of thyroid hormone in the medium. (6) Taken together, results suggest thyroid hormone causes a selective increase in [(125)I]PIN binding to beta(2)-AR due to increase in receptor affinity, which may lead to maturation of astrocytes.
Ghosh
Mausam
M
Indian Institute of Chemical Biology, Jadavpur, Kolkata, 700032, India.
Das
Sumantra
S
D058672:Adrenergic beta-2 Receptor Antagonists; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002478:Cells, Cultured; D006801:Humans; D007037:Hypothyroidism / Q000378:metabolism / Q000473:pathology; D010869:Pindolol / Q000493:pharmacokinetics; D011485:Protein Binding / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism*; D013379:Substrate Specificity / Q000187:drug effects; D013963:Thyroid Hormones / Q000494:pharmacology*; D014162:Transfection