Thyroid-stimulating hormone neurotransmitter effect

Li+ has been reported to affect virtually every component of the endocrine system to some extent however any resulting clinical manifestations are very rare [169]. Although these influences do not appear to be related to its mechanism of action in manic-depression, some are involved in the side effects experienced by Li+-treated patients. Apart from elevated levels of thyroid stimulating hormone (TSH), Li+ does not appear to affect the basal levels of hormones significantly however some hormone responses are reported to be altered by Li+ treatment of bipolar patients [170]. Neuronal activity stimulates the adrenal medulla to release norepinephrine and epinephrine into the blood and, consequently, the plasma from people with mania and depression shows increased levels of both neurotransmitters [171]. 

Many of the adverse effects of lithium can be ascribed to the action of lithium on adenylate cyclase, the key enz)nne that links many hormones and neurotransmitters with their intracellular actions. Thus antidiuretic hormone and thyroid-stimulating-hormone-sensitive adenylate cyclases are inhibited by therapeutic concentrations of the drug, which frequently leads to enhanced diuresis, h)rpoth)n oidism and even goitre. Aldosterone synthesis is increased following chronic lithium treatment and is probably a secondary consequence of the enhanced diuresis caused by the inhibition of antidiuretic-hormone-sensitive adenylate cyclase in the kidney. There is also evidence that chronic lithium treatment causes an increase in serum parathyroid hormone levels and, with this, a rise in calcium and magnesium concentrations. A decrease in plasma phosphate and in bone mineralization can also be attributed to the effects of the drug on parathyroid activity. Whether these changes are of any clinical consequence is unclear. 

The hypothalamus contains high concentrations of the monoamines dopamine and serotonin and these neurotransmitters have inhibitory or excitatory effects, respectively, on the anterior pituitary. For example, thyroid-stimulating hormone (TSH) secretion is increased by serotoninergic and decreased by dopaminergic activation. Pyridoxine deficiency in rats is associated with low levels of PLP in the hypothalamus, with no change in dopamine concentrations, but decreased levels of serotonin (Dakshinamurti et al., 1990). This correlates with decreased thyroid status and decreased pituitary TSH. Treatment with pyridoxine returns these parameters to normal. 

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