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

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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/