Inositol monophosphate esterase inhibition by lithium in normal human studies using neuroendocrine tests. Part I. PRL...

1. Many neuroendocrine events are mediated by intracellularly second messengers, among which are the breakdown of phosphatidylinositol 4,5-biphosphate (PIP2). 2. Lithium (Li) was shown in therapeutic doses to be a specific inhibitor of the enzyme inositol monophosphate esterase Li reduces the turnover of PIP2 and diminishes the cell responses. 3. In order to investigate this new mode of action of Li the authors studied the influence of acute dose of Li on the response of prolactin (PRL) and thyrotropin (TSH) to thyrotropin stimulating hormone (TRH), a stimulation mainly mediated through the activation of the turnover of PIP2. 4. In seven normal subjects a single dose of 19.80 meq of Li reduced the response of PRL in 4, and augmented it in 3 subjects: Li decreased the TSH response in 4 subjects, it was increased in 1 and remained unchanged in 2. 5. These results are discussed in the light of the different interactions between hormone secretion, and the fact that adenopituitary is located out of the brain blood barrier.