REGULATION OF ACTIN AND ITS MESSENGER-RNA BY THYROID-HORMONES IN CULTURES OF FETAL HUMAN BRAIN DURING 2ND-TRIMESTER OF GESTATION

The effect of thyroid hormones (THs) on the expression of actin gene d uring fetal human brain development and the period of sensitivity to t he hormones have been investigated, Developmental profile of ac tin in the cytoskeletal (CSK) and noncytoskeletal (non-CSK) fractions in the fetal cerebra showed a pronounced rise in the level of CSK actin at w eeks 17-19. Northern blot analysis also revealed a sharp rise in the l evel of actin mRNA at weeks 16-18, temporally coinciding with the peri od of rise of THs and peak expression of TH receptors in the fetal bra in. In organ cultures of weeks 13-23 fetal cerebra, THs elicited a gen eral stimulation of CSK proteins at all ages studied with a preferenti al effect on actin at weeks 17-19. During this period, THs also stimul ated 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 feta l 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 i nsoluble CSK fraction, suggesting an effect of the hormone on the intr acellular distribution of actin between the soluble non-CSK fraction a nd 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 regula te the expression of actin gene by stimulating the rate of synthesis a s well as intracellular distribution of actin during the mid phase of the second trimester of gestation.