Thyroid hormone-induced morphological differentiation and maturation of astrocytes are mediated through the beta-adrenergic receptor.
The molecular mechanisms associated with thyroid hormone (TH)-induced maturation of astrocytes have been studied using primary cultures. We have previously demonstrated that unlike normal astrocyte cultures, hypothyroid cultures fail to differentiate from flat polygonal cells with epithelioid morphology into mature process-bearing cells with stellate morphology. Addition of TH to the hypothyroid cells reverses the effect, and astrocytes transform into stellate cells. The beta-adrenergic receptor (beta-AR) agonist isoproterenol (ISP) has a similar effect, whereas simultaneous addition of the beta-adrenergic antagonist propranolol blocks the differentiation induced by TH or ISP. Addition of TH or ISP to hypothyroid cultures is also associated with a decrease in the level of filamentous cytoskeletal (F(i)) actin and an increase in the level of actin mRNA. Although addition of propranolol inhibited the decline in the level of F(i) actin in the TH- or ISP-supplemented cells as well as the induction of actin mRNA by TH, it partially inhibited the ISP-induced actin mRNA in these cultures. The hormone-induced maturation appears to be selectively regulated through the beta(2)-AR. The overall results indicate that the beta-adrenergic system plays an obligatory role in promoting TH-induced differentiation and maturation of astrocytes and in regulating the hormone-induced expression of actin and its intracellular organization in a way conducive to the morphological differentiation of the cells.
Gharami
K
K
Neurobiology Division, Indian Institute of Chemical Biology, Calcutta, India.
Das
S
S
D000199:Actins / Q000032:analysis / Q000235:genetics / Q000378:metabolism; D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000420:Albuterol / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D002454:Cell Differentiation / Q000187:drug effects; D002458:Cell Fractionation; D002478:Cells, Cultured; D003599:Cytoskeleton / Q000737:chemistry / Q000378:metabolism; D003902:Detergents / Q000737:chemistry; D007037:Hypothyroidism / Q000378:metabolism*; D007545:Isoproterenol / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D013963:Thyroid Hormones / Q000378:metabolism* / Q000494:pharmacology
D000199:Actins; D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D000319:Adrenergic beta-Antagonists; D003902:Detergents; D012333:RNA, Messenger; D011943:Receptors, Adrenergic, beta; D013963:Thyroid Hormones; D011433:Propranolol; D007545:Isoproterenol; D000420:Albuterol; D009638:Norepinephrine