Tyrosine Content, Influx and Accumulation Rate, and Catecholamine Biosynthesis Measuredin Vivo, in the Central Nervous System and in Peripheral Organs of the Young Rat. Influence of Neonatal Hypo- and Hyperthyroidism

Abstract

The influence of neonatal hypo- and hyperthyroidism on different aspects of tyrosine metabolism in the hypothalamus, striatum, brainstem, adrenal glands, heart and brown adipose tissue (BAT) were studied in 14-day old rats. The synthesis rate of catecholamines (CA) was also determined in vivo after the injection of labelled tyrosine. Hypothyroidism increases tyrosinaemia and endogenous tyrosine concentration in the hypothalamus and BAT. Hyperthyroidism decreases tyrosinaemia and endogenous tyrosine levels in the striatum, adrenals and heart. The accumulation rate of tyrosine determined 30 min after an intravenous injection of the labelled amino acid has been determined in the organs, together with the influx of the amino acid, determined within 20s. Hypothyroidism increases tyrosine accumulation rate in all the organs studied, and tyrosine clearance is decreased in the striatum and brainstem; together with an increased tyrosinaemia, this leads to a normal influx. The influx of tyrosine is increased in the hypothalamus. Hyperthyroidism decreases tyrosine accumulation rate in all the organs except the adrenals. These results indicate that the thyroid status of the young rat can influence tyrosine uptake mechanisms, without modifying an organ's tyrosine content. The fact that hypothyroidism increases tyrosine influx in the hypothalamus without modifying it in the brainstem and striatum reflects an heterogeneous reactivity to the lack of thyroid hormones in different brain structures. Neonatal hypothyroidism decreases the CA synthesis rate in the striatum, the heart and the interscapular brown adipose tissue, while synthesis was enhanced in the brainstem and the adrenals. It is likely that these variations in CA synthesis are due to thyroid hormone modulation of tyrosine hydroxylase activity, the enzyme which catalyses the rate limiting step in CA biosynthesis.

Thyroid hormone modulation of brain in vivo tyrosine hydroxylase activity and kinetics in the female catfish Heteropneustes fossilis

“…Hypothyroidism caused tyrosinaemia (tyrosine accumulation) in the brain, adrenal, heart, etc. (Diarra et al 1989) and the genetically hypothyroid mouse (non-functional thyroid due to defective TSH receptor) showed significantly fewer (40%) dopamine (TH-positive) neurons in the substantia nigra and adjacent ventral tegmental area (Kincaid 2001). The reported effects of hypothyroidism on TH are at variance and seem to be influenced by several factors including its nature of induction.…”

Revisiting Thyroid Hormones in Schizophrenia

“…Thyroid hormones have been shown to regulate the levels of dopamine receptors [74, 75] and the activity of tyrosine hydroxylase [76–78], the rate-limiting enzyme of the cathecolaminergic pathway. Moreover, it has been suggested that dopamine may be inhibitory of TSH secretion [59], as treatment with dopamine blockers lead to increase in TSH level or to subclinical hypothyroidism [79], and that hypothyroidism can lead to increased dopamine receptor sensitivity [74].…”

Amine oxidase activity of β-amyloid precursor protein modulates systemic and local catecholamine levels

“…7 Stored in specialized cellular vesicles until required, the catecholamines dopamine (DA) and norepinephrine (NE) predominantly act as neurotransmitters within the brain, whereas NE and another catecholamine derived from DA, epinephrine (E), are the major peripheral catecholamines synthesized in the medulla of the adrenal gland. 8 Endogenous production of catecholamines has also been found in the heart, 9,10 immunocompetent cells, 6 gut 11 and kidneys. 12,13 Upon release of catecholamines during neurotransmission in the brain, mechanisms around the synapse clear 80-90% of the neurotransmitter, but spillover of excess catecholamines may act on targets at a distance and enter plasma.…”