Effect of Thyroid on Fatty Acid Biosynthesis in Brain

Abstract

ExtractTriodothyronine (T 3 ) was given daily by injection to rats from 1 day of age to 2 hr prior to death. In the brain microsomal fraction of 5-to 6-day-old animals, incorporation of malonyl-CoA into total fatty acids increased from 0.9 to 2.25 m/imoles/mg protein. Although thyroid increased precursor incorporation into total fatty acids in other age groups, the difference was not statistically significant. Increased precursor incorporation was entirely due to increased formation of saturated fatty acids, and this effect was observed at all age groups.Incorporation of acetyl-CoA into saturated and unsaturated fatty acids by the mitochondrial fraction was not increased significantly by administration of T 3 .In rats made hypothyroid at birth, fatty acid chain elongation was reduced in both the microsomal and the mitochondrial fractions. At 6 days of age, incorporation of malonyl-CoA by the microsomal fraction fell from 1.41 to 0.17 m/imoles/mg protein. These studies suggest that thyroid stimulates the microsomal-fatty acid-brain elongation system involved in the synthesis of saturated fatty acids characteristic of myelin lipids. SpeculationThe stimulation of fatty acid biosynthesis by thyroid hormone is specifically limited to the synthesis of saturated fatty acids by the microsomal fraction. Since the effect of thyroid is probably mediated by enzyme synthesis, we conclude that the microsomal fraction contains two distinct enzyme systems involved in fatty acid chain elongation, one for the formation of polyunsaturated fatty acids, the other for the formation of saturated fatty acids. The activity of the latter system increases at time of myelination, and as a consequence of thyroid stimulation.

Growth and Development of the Thyroidectomized Ovine Fetus

“…Inasmuch as the ovine fetal thyroid begins t o function at about 50 days gestation ( 5 ) and the fetuses were presumably euthyroid between 5 0 and 90-110 days, the extent of thyroxine dependence of early ovine fetal brain development is not clear. However, the present data are in general agreement with an earlier report of Grippo and Menkes (21) which showed that fatty acid elongation was reduced in rats made hypothyroid at birth. These authors suggested that iodothyronines may stimulate the brain microsomal-fatty acid elongation system involved in the synthesis of saturated fatty acids characteristic for myelin lipids.…”

“…Its chemical properties (for review see Reference 8) and variations of the plasma levels of the factor in different pathologic conditions have been the subject of several studies (e.g., 11,13,18,19,22). For newborn infants, some authors reported low values (1, 3, 7, 23), whereas others have found normal adult levels (6,14,17,21,24). However, all of these investigations were carried out with bioassays, such as differential clot solubilities, which from the quantitative point of view are of questionable reliability.…”

Thyroid-Dependent Maturation of Neonatal Brain but Not Lung Epidermal Growth Factor Receptors

“…On the other hand, the effect of thyroxine (T4) in the developing brain metabolism is well established [24][25][26]. T4 augments brain cholesterol [24] and fatty acid synthesis [25] while T4 defi ciency retards dendritic arborization and myelination [26].…”