Endocrine Abstracts (2001) 2 P103

Maternal hyperthyroidism disrupts neuronal development in late fetal brain

IM Evans, MR Pickard, AK Sinha, DC Sampson, AJ Leonard & RP Ekins

Molecular Endocrinology, UCL Medical School, London, UK.

Maternal hypothyroidism disrupts fetal brain development in the rat; affected parameters include several neuron-specific cytoskeletal proteins and neurotransmitter metabolic enzymes. The aim of this study was to determine whether maternal hyperthyroidism also impacts upon fetal neuronal development.

Partially thyroidectomised rat dams were subcutaneously implanted with osmotic pumps to infuse either 1.5 micrograms thyroxine/100 g body weight/day (HYPER) or vehicle (TX). Age-matched normal dams were also implanted with pumps infusing vehicle (N). Fetal brains were obtained at 21 days gestation and alpha-internexin (INX) and neurofilament-68 (NF68) protein abundance were determined by Western blot analysis, and neuronal and glial isoforms of monoamine oxidase (MAO-A and -B, respectively) were determined by conventional enzyme assays. Data (n = 4 dams per group) were analysed by one-way ANOVA with Fisher's PLSD.

Relative to N dams, maternal serum thyroxine levels were increased (by 176%; P < 0.05) in HYPER dams and decreased in TX dams (by 82% P < 0.05). Fetal brain weights were increased in HYPER dams versus N dams (by 15%; P < 0.05), but fetal brain protein and DNA concentrations were unaffected. Relative to TX dam fetal brain, INX expression was lower (by 62%; P < 0.05) in HYPER dam fetuses and, conversely, NF68 expression was increased (by 60%; P < 0.05), although clear-cut differences between HYPER or TX dams and N dams were not apparent for these parameters. However, the specific activity of MAO-A was increased (by 30%) in HYPER dams relative to N and TX dams (P < 0.05), whereas MAO-B was unaffected.

In summary, preliminary findings indicate that maternal hyperthyroidism throughout pregnancy in the rat is associated with accelerated neuronal development in late fetal brain.

This work was funded by a grant from Action Research.

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