Hypothyroidism of hypothalamic origin in pyridoxine-deficient rats

Pyridoxine-deficient young rats (3 weeks old) had significantly reduced levels of pituitary TSH, serum thyroxine (T4) and tri iodothyn nine (T,,) Compared with pyridoxine-supplemented rats. The status of the pituitary-thyroid axis of normal, pyridoxine-supplemented and pyridoxine-deficient rats was evaluated by studying the binding parameters of [3H](3-nicthylhistidine2) TRH in the pituitary of these rats. The effects of TRH and 1'4 injections on pituitary TSH and serum TSH, T4 and T3 of these two groups were also compared. The maximal binding of TRH receptors in the pituitary of pyridoxine-deficient rats was significantly higher than that of pyridoxine-supplemented control and normal rats, but there was no change in the binding affinity. Treatment with TRH stimulated TSH synthesis and release. It also increased serum T4 and T3 in both pyridoxine-supplemented and pyridoxine-deficient rats. Treatment with T4 decreased serum and pituitary TSH in both pyridoxine-supplemented and pyridoxine-deficient rats, compared with saline-treated rats. The increased pituitary TRH receptor content, response to TRH administration and the fact that regulation at the level of the pituitary is not affected in the pyridoxinedeficient rat indicates a hypothalamic origin for the hypothyroidism of the pyridoxine-deficient rat.

Neuroendocrinology of Pyridoxine Deficiency

Veuruenducrim lri v j p .rim, deficienc:v. NEUROSCI BIOBEHAV REV 12(3/4) 189-193. 1988.- Dihydroxyphenylalanine decarboxvlase and 5-hydroxytryptophan decarboxvlase respectively have high and low affinities for pyridoxal phosphate. In the pyridoxinedeficient animal. hypothalamic serotonin content is significantly reduced without any change in catecholamine levels. Hypothalamic neurotransmitters affect the hvpothalamo-pituitary-end organ axes. Specifically, the decrease in hypothalamic serotonin in the pyridoxine-deficient rat results in tertiary hypothyroidism. In addition. pineal function is affected in deficient animals due to decreased synthesis of melatonin.

Sympathetic Stimulation and Hypertension in the Pyridoxine-Deficient Adult Rat

Pyridoxal phosphate is the coenzyme of various decarboxylases involved in the formation of monoamine neurotransmitters such as y-aminobutyric acid , serotonin , dopamine, and norepinephrine . Adult male Sprague-Dawley rats placed on a pyridoxine -deficient diet for 8 weeks showed significant hypertension compared with pyridoxine -supplemented controls . Hypothalamic contents of pyridoxal phosphate , y-aminobutyric acid, and serotonin in the pyridoxine - deficient rats were significantly lower than those in pyridoxine -supplemented controls . Hypertension was associated with sympathetic stimulation . Treatment of pyridoxine-deficient rats with a single dose of pyridoxine (10 mg/kg body weight) reversed the blood pressure to normal levels within 24 hours, with concomitant restorations of hypothalamic serotonin and y-aminobutyric acid as well as the return of plasma norepinephrine and epinephrine to normal levels . Also, pyridoxine treatment reversed the hypothalamic hypothyroidism observed in pyridoxine -deficient rats . These results indicate an association between pyridoxine deficiency and sympathetic stimulation leading to hypertension.