The stimulatory effect of chronic lithium treatment on basal thyrotropin secretion in rats: in vivo antagonism by methylparaben.
Chronic treatment of rats with lithium chloride was examined in order to determine its effects on hypothalamic monoamine and metabolite content, basal thyrotropin (TSH) secretion and thyroid function. The hypothalamic concentrations of noradrenaline (NA), dopamine (DA) and its metabolites, dihydroxyphenylacetic acid. (DOPAC) and homovanillic acid (HVA) in the lithium treated rats remained unaltered when compared to control levels. NA turnover and the NA metabolite, 3-methoxy-4-hydroxyphenylglycol (total MHPG), were significantly lower (p < 0.01), whereas both serotonin (5-HT) and its metabolite, 5-hydroxyindole-3-acetic acid (5-HIAA), were significantly higher (p < 0.01 and p < 0.02, respectively) in the lithium treated rat hypothalami than in controls. Chronic lithium treatment significantly elevated basal TSH levels (p < 0.05). This effect was antagonized by methyl p-hydroxybenzoate (methylparaben, p < 0.01), which did not itself affect basal TSH levels. Free serum T3 and T4 levels were not significantly affected by chronic lithium treatment, although T4 tended to be slightly lower than control levels. The monoamine changes observed in the hypothalamus of lithium treated rats did not appear to account for the elevated TSH levels observed in these rats since NA activity which is generally regarded as stimulatory was decreased and 5-HT which has an inhibitory effect on TSH secretion, was increased. The elevated TSH levels may have been due to a reduced negative feedback inhibition of TSH release by the mildly reduced circulating T4 levels caused by chronic lithium treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Jaffer
A
A
Department of Chemical Pathology, University of Stellenbosch, Tygerberg Hospital, R.S.A.
Harvey
B
B
Russell
V A
VA
Carstens
M E
ME
de Villiers
A S
AS
Taljaard
J J
JJ
D000818:Animals; D004298:Dopamine / Q000378:metabolism; D006897:Hydroxyindoleacetic Acid / Q000378:metabolism; D007031:Hypothalamus / Q000187:drug effects* / Q000502:physiology; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000378:metabolism; D009638:Norepinephrine / Q000378:metabolism; D010226:Parabens / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012701:Serotonin / Q000378:metabolism; D013972:Thyrotropin / Q000378:metabolism*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D013974:Thyroxine / Q000097:blood; D014284:Triiodothyronine / Q000097:blood
D010226:Parabens; D014284:Triiodothyronine; D012701:Serotonin; D008734:Methoxyhydroxyphenylglycol; D006897:Hydroxyindoleacetic Acid; D013973:Thyrotropin-Releasing Hormone; D013972:Thyrotropin; D008094:Lithium; C015358:methylparaben; D013974:Thyroxine; D004298:Dopamine; D009638:Norepinephrine