GABA inhibits thyroid hormone secretion in the mouse.
The enzymes responsible for both the formation and degradation of gamma-aminobutyric acid (GABA) are known to exist in the thyroid gland. The thyroid is also equipped with high- and low-affinity uptake mechanisms for GABA. We therefore investigated the effects of GABA on basal and TSH-stimulated thyroid hormone secretion in the mouse according to the McKenzie technique. Iodine-deficient mice were pretreated with Na125I and thyroxine. GABA (1-100 nmol/kg iv) did not affect basal radioiodine levels. However, the neurotransmitter inhibited the TSH-induced increase in blood radioiodine levels. Thus, the increase after iv injection of TSH at 70 microU/animal (205 +/- 15%) was inhibited by GABA at 10 nmol/kg (to 155 +/- 14%; P less than 0.05). In contrast, a dose as high as 100 nmol/kg was necessary to inhibit the effect of TSH at its high dose of 350 microU/animal. The GABAA-receptor antagonist bicuculline counteracted this inhibitory action of GABA. Furthermore, pretreatment with the inhibitor of GABA-degrading enzyme GABA transaminase (gamma-vinyl GABA) impaired the stimulatory effect of TSH on blood radioiodine levels. Thus, at 350 microU/animal, TSH increased blood radioiodine levels by 363 +/- 34% in controls vs by only 246 +/- 32% in animals pretreated with gamma-vinyl-GABA (P less than 0.05). We conclude that GABA is an inhibitor of TSH-stimulated thyroid hormone secretion.
Ahrén
B
B
Department of Pharmacology, Lund University, Sweden.
D000612:4-Aminobutyrate Transaminase / Q000037:antagonists & inhibitors; D000614:Aminocaproates / Q000494:pharmacology; D000818:Animals; D001640:Bicuculline / Q000494:pharmacology; D005260:Female; D051379:Mice; D011963:Receptors, GABA-A / Q000187:drug effects; D013961:Thyroid Gland / Q000187:drug effects / Q000378:metabolism; D013963:Thyroid Hormones / Q000378:metabolism*; D013972:Thyrotropin / Q000494:pharmacology; D020888:Vigabatrin; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000494:pharmacology*
D000614:Aminocaproates; D011963:Receptors, GABA-A; D013963:Thyroid Hormones; D005680:gamma-Aminobutyric Acid; D013972:Thyrotropin; D000612:4-Aminobutyrate Transaminase; D020888:Vigabatrin; D001640:Bicuculline