The effect of thyroid hormone on serotonergic neurones: depletion of serotonin in discrete brain areas of developing hypothyroid rats.
A single intraperitoneal injection of 131I in a dose of 200muCi in 1-day-old rats induced hypothyroidism and decreased the activity of tryptophan hydroxylase in mid-brain region. The levels of 5-hydroxytryptamine also were reduced in cerebellum, mid-brain and striatum by 22%, 29% and 31%, respectively. By contrast, the levels of its metabolite, 5-hydroxyindoleacetic acid, were significantly increased in cerebellum, mid-brain and striatal region. To ascertain whether changes induced by neonatal radiothyroidectomy were specific, the effect of replacement thyroid hormone therapy was studied on 5-hydroxytryptamine metabolism. Daily administration of L-triiodothyronine (10 microgram/100g s.c.) for 25 days beginning from five days after radio-iodine treatment enhanced tryptophan hydroxylase activity, tryptophan and 5-hydroxytryptamine levels to values seen in normal rats of the corresponding age group. The concentration of 5-hydroxyindoleacetic acid decreased following L-triiodothyronine treatment. Furthermore, when replacement therapy with L-triiodothyronine was postponed until adulthood, no significant effects could be seen on various parameters related to 5-hydroxytryptamine metabolism. Our data demonstrate that deficiency of thyroid hormone in early life disrupts the normal upsurge of 5-hydroxytryptamine metabolism in brain. A critical period exists in early life of rats during which thyroid hormone must be present for the optimal development of 5-hydroxytryptamine metabolizing systems in maturing brain.
D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007037:Hypothyroidism / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy; D051381:Rats; D012701:Serotonin / Q000378:metabolism*; D013965:Thyroidectomy; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D012701:Serotonin; D006897:Hydroxyindoleacetic Acid