Regulation of actin and its mRNA by thyroid hormones in cultures of fetal human brain during second trimester of gestation

Abstract

The effect of thyroid hormones (THs) 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, THs also stimulated the rate of synthesis of actin. Kinetics of induction of actin by TH in the non-CSK and CSK fractions 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 CSK fraction. Correspondingly, in cultures of week 17 fetal cerebra, THs elicited an increase in actin mRNA level within 30 min 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.