title: Effect of maternal hypothyroxinaemia in the rat on brain biochemistry in adult progeny.
abstract: The effects of maternal hypothyroxinaemia during pregnancy on subsequent brain biochemistry in progeny was studied. Normal and partially thyroidectomized rat dams were mated and progeny allowed to grow to adulthood. Brain regions (cerebellum, medulla, midbrain, cerebral cortex and paleocortex) were dissected out and the activities of various cell marker enzymes were determined, along with cholesterol contents. Maternal hypothyroxinaemia was without effect on body weight, brain weight or thyroid status of adult progeny. Oligodendroglial marker enzyme activities were altered in progeny from thyroidectomized dams. 2',3'-Cyclic nucleotide 3'-phosphohydrolase was decreased in the medulla (by 37%) and midbrain (by 32%). 5'-Nucleotidase was also diminished in the same brain regions, by 33% in the medulla and by 35% in the midbrain. In contrast, oleate esterase was increased (by 39%) in the paleocortex. Although these enzymes are putatively involved in myelin metabolism, no changes were observed in the concentration of a major myelin lipid (cholesterol). The activity of beta-D-glucuronidase (a general neuronal marker) was decreased (by 30%) in the paleocortex, whereas N-acetyl-beta-D-galactosaminidase (a general glial marker) was unchanged in all brain regions. In summary, maternal hypothyroxinaemia has irreversible effects on brain biochemistry in adult progeny. The damage is parameter-selective and brain region-specific, analogous to the pattern of neurological damage seen in offspring born to hypothyroxinaemic women in iodine-deficient endemias.
authors.affiliation: Department of Molecular Endocrinology, University College and Middlesex School of Medicine, London.
authors.forename: M
authors.initials: M
authors.lastname: Hadjzadeh
authors.forename: A K
authors.initials: AK
authors.lastname: Sinha
authors.forename: M R
authors.initials: MR
authors.lastname: Pickard
authors.forename: R P
authors.initials: RP
authors.lastname: Ekins
mesh_terms: D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases / Q000378:metabolism; D015720:5'-Nucleotidase / Q000378:metabolism; D000118:Acetylglucosaminidase / Q000378:metabolism; D000818:Animals; D001835:Body Weight; D001921:Brain / Q000033:anatomy & histology / Q000378:metabolism*; D002784:Cholesterol / Q000378:metabolism; D005260:Female; D005966:Glucuronidase / Q000378:metabolism; D008297:Male; D009929:Organ Size; D010727:Phosphoric Diester Hydrolases; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood*; D051381:Rats; D011919:Rats, Inbred Strains; D002787:Sterol Esterase / Q000378:metabolism; D013965:Thyroidectomy; D013974:Thyroxine / Q000097:blood*
chemical_list: D002784:Cholesterol; D002787:Sterol Esterase; D015720:5'-Nucleotidase; D015087:2',3'-Cyclic-Nucleotide Phosphodiesterases; D010727:Phosphoric Diester Hydrolases; D063309:2',3'-Cyclic Nucleotide 3'-Phosphodiesterase; C571339:Cnp protein, rat; D005966:Glucuronidase; D000118:Acetylglucosaminidase; D013974:Thyroxine