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Regulation of Actin and Its mRNA by Thyroid Hormones in Cultures of Fetal Human Brain During Second Trimester of Gestation

IR@IICB: CSIR-Indian Institute of Chemical Biology, Kolkata

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Title Regulation of Actin and Its mRNA by Thyroid Hormones in Cultures of Fetal Human Brain During Second Trimester of Gestation
 
Creator Pal, Utpal
Biswas, Subhas C
Sarkar, Pranab K
 
Subject Chemistry
 
Description The effect of thyroid hormones (TH5) on the expression of actin gene during fetal human brain development and the period of sensitivity to the hormones have been investigated. Developmental profile of actin in the cytoskeletal (CSK) and noncytoskeletal (non-CSK) fractions in the fetal cerebra showed a pronounced rise in the level of CSK actin at weeks 17—19. Northern blot analysis also revealed a sharp rise in the level of actin mRNA at weeks 16—18, temporally coinciding with the period of rise of THs and peak expression of TH receptors in the fetal brain. In organ cultures of weeks 13—23 fetal cerebra, THs elicited a general stimulation of CSK proteins at all ages studied with a preferential effect on actin at weeks 17—19. During this period, TH5 also stimulated the rate of synthesis of actin. Kinetics of induction of actin by TH in the non-CSK and CSKfractions in organ cultures of week 17 fetal cerebra showed an increased level of actin in both fractions within 1 h. Subsequently (at 5 and 18 h), induction was evident only in the insoluble CSK fraction, suggesting an effect of the hormone on the intracellular distribution of actin between the soluble non-CSK fraction and the insoluble CSKfraction. Correspondingly, in cultures of week 17 fetal cerebra, THs elicited an increase in actin mRNA level within 30 mm of hormonal exposure. The overall results suggest that THs regulate the expression of actin gene by stimulating the rate of synthesis as well as intracellular distribution of actin during the mid phase of the second trimester of gestation. Key Words: Thyroid hormone—Actin—Human fetal brain—Gene expression. and hearing or speech disabilities (Glorieux et al., 1983) apart from other mild to significant neurological abnormalities (Birrell et al., 1983; Rovet et al., 1984). However, little is known concerning the molecular events associated with the effect of THs in human brain development, because most of the experimental studies have been performed with prenatal or postnatal animals (Dussault and Ruel, 1987). Although the sequence of neurodevelopmental events is identical in rats and humans, the time spans of these events are quite different and much more prolonged in humans. High-affinity nuclear TH receptors as well as triiodothyronine (T3) appear in human fetal brain as early as week 11 of gestation, but their concentration undergoes a dramatic increase at midgestation during weeks 16—18 (Bernal and Pekonen, 1984; Karmarkar et al., 1990). Other evidence indicates that the critical event of neurite outgrowth and elongation, which leads to synaptogenesis in human brain, is also initiated during the second trimester of gestation (Delong, 1989; Stein et al., 1989; Ulfig, 1992). Earlier investigations with rat brain led to the identification of several target proteins such as actin (De et al., 1991), tubulin (Chaudhury et al., 1985), epidermal growth factor.
 
Date 1997
 
Type Article
PeerReviewed
 
Format application/pdf
 
Identifier http://www.eprints.iicb.res.in/803/1/JOURNAL_OF_NEUROCHEMISTRY%2C_69_(_3)%2C1170%2D1176_[31].pdf
Pal, Utpal and Biswas, Subhas C and Sarkar, Pranab K (1997) Regulation of Actin and Its mRNA by Thyroid Hormones in Cultures of Fetal Human Brain During Second Trimester of Gestation. Journal of Neurochemistry, 69 (3). pp. 1170-1176.
 
Relation http://dx.doi.org/10.1046/j.1471-4159.1997.69031170.x
http://www.eprints.iicb.res.in/803/