Lithium induces corticotropin secretion and desensitization in cultured anterior pituitary cells.

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Abstract
Li stimulated ACTH secretion by mouse pituitary tumor cells (AtT-20/D16-16) and by normal rat anterior pituitary cells in primary culture. Effects were observed at less than 2 mM LiCl. ACTH secretion was comparable in magnitude to that induced by other secretgogues, was Ca dependent, and was inhibited by somatostatin. Li also induced changes in [3H]inositide metabolism; these changes accompanied and were correlated with changes in ACTH secretion. The most prominent and reliable effect was to increase (3H]inositol monophosphate. Other secretagogues had no effect on [3h]inositides in the presence or absence of Li. Pretreatment with Li for 3 h desensitized the cells to the effects of subsequent exposure to Li. The cells were not desensitized to Li by pretreatment with other secretagogues, nor were they desensitized by Li to the effects of ACTH-releasing factor, high K, or forskolin. Pretreatment with Li did desensitize the cells to stimulation by phorbol esters. The interaction between Li and phorbol esters suggests the involvement of inositide metabolism and protien kinase C in the regulation of ACTH secretion and possibly of other hormones or neurotransmitters. It also suggest s new avenues of research into the basis of Li psychopharmacological effects.